Updated on 2025/09/17

写真a

 
YOSHIBA Nagako
 
Organization
Academic Assembly Institute of Medicine and Dentistry SHIGAKU KEIRETU Professor
Graduate School of Medical and Dental Sciences Oral Health and Welfare Science Oral Health and Welfare Professor
Title
Professor
External link

Degree

  • 博士(歯学) ( 1996.6   新潟大学 )

Research Areas

  • Life Science / Conservative dentistry

Research History (researchmap)

  • 新潟大学大学院医歯学総合研究科 口腔保健学分野 教授

    2024.4

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  • Niigata University   研究推進機構研究准教授

    2022.11 - 2024.3

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  • 2021年度拠点事業「大阪大学蛋白質研究所共同研究員」

    2021.4 - 2022.3

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  • 新潟大学医歯学総合病院 講師

    2009.4 - 2024.3

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  • 日本学術振興会海外特別研究員 ルイパスツール・ストラスブルブ大学（フランス）

    2002.4 - 2003.1

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  • 新潟大学歯学部 助手

    2000.1 - 2009.3

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  • 日本学術振興会特別研究員（PD）

    1997.4 - 1999.12

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  • ルイパスツール・ストラスブルグ大学（フランス）リサーチフェロー

    1995.11 - 1996.10

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  • 新潟大学歯学部付属病院 医員

    1989.4 - 1995.10

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Research History

  • Niigata University   Institute of Medicine and Dentistry, Academic Assembly   Professor

    2024.4

  • Niigata University   Dental Educational Research Development, Master's Program of Oral Health and Welfare Science, Graduate School of Medical and Dental Sciences   Professor

    2024.4

  • Niigata University   University Medical and Dental Hospital Dental Health   Lecturer

    2009.4 - 2024.3

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science   Lecturer

    2009.4 - 2024.3

  • Niigata University   Graduate School of Medical and Dental Sciences Oral Life Science   Assistant Professor

    2004.4 - 2009.3

Education

  • Niigata University   Faculty of Dentistry   School of Dentistry

    - 1989

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    Country： Japan

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  • Niigata University   Faculty of Dentistry

    - 1989

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Professional Memberships

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Papers

  • Macrophage induces angiogenesis via HIF signaling in denervated muscle following nerve injury Reviewed

    Yurie Sato-Yamada, Meircurius Dwi Condro Surboyo, Andrea L. Rosenkranz, Tomoaki Ujita, Meiwen Fang, Prasiddha Mahardhika EI Fadhlallah, Tomoki Maekawa, Yumiko Sato, Nagako Yoshiba, Takeyasu Maeda

    Scientific Reports   15 ( 1 )   2025.7

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    Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    DOI： 10.1038/s41598-025-07536-y

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    Other Link： https://www.nature.com/articles/s41598-025-07536-y

  • The effects of Zoledronate administration routes on the reproducibility of BRONJ in rodent models: A systematic review Reviewed

    Meircurius Dwi Condro Surboyo, Prasiddha Mahardhika El Fadhlallah, Yurie Sato-Yamada, Kridtapat Sirisereephap, Fang Meiwen, Takeyasu Maeda, Kei Tomihara, Koichi Tabeta, Nagako Yoshiba, Andrea L. Rosenkranz, Tomoki Maekawa

    Bone   117563 - 117563   2025.6

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.bone.2025.117563

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  • Loss of integrin alpha7-mediated signaling induces a dendritic cell-like phenotype in macrophages cultured on laminin-211/221 isoforms Reviewed

    Nagako Yoshiba, Tomoki Maekawa, Kiyotoshi Sekiguchi, Masaru Kaku, Kridtapat Sirisereephap, Meircurius Surboyo, Yurie Sato-Yamada, Andrea Rosenkranz, Akihiro Hosoya, Naoto Ohkura, Yoshito Kakihara, Takeyasu Maeda, George Hajishengallis, Kenji Izumi, Kunihiko Yoshiba

    Journal of Biological Chemistry   110419 - 110419   2025.6

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.jbc.2025.110419

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  • Influence of Tooth Maturity on Healing Outcomes in Regenerative Endodontics Reviewed

    S. Takahara, N. Ohkura, N. Yoshiba, R. Baldeon-Gutierrez, S. Gomez-Kasimoto, N. Edanami, T. Ida, S. Takenaka, K. Yoshiba, Y. Noiri

    Journal of Dental Research   2025.4

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    Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

    Regenerative endodontic procedures using blood clots (BC-REP) for immature teeth typically exhibit a periodontal ligament–like healing pattern. However, a pulp-like healing pattern is observed in the presence of residual pulp. This study aimed to clarify the healing phenotype according to tooth maturity when performing BC-REP in the presence of residual pulp, focusing on migrated mesenchymal stem/stromal cells (MSCs). BC-REP rat molar models were created in the presence of residual pulp at ages corresponding to tooth developmental stages, from immature to mature (5 wk: immature, root is still growing; 8 wk: near mature, root has finished growing in length but the apex is not formed; 11 wk: mature, the apex is formed). The healing pattern and histological MSC markers (α–smooth muscle actin [α-SMA], CD73, CD90, and CD146) were investigated. The frequency of periodontal ligament–like healing was higher in mature teeth than in immature teeth. In addition, more healing macrophages were observed at the apical site 28 d after BC-REP, which is the final stage of healing. In immature teeth, double-immunopositive cells for proliferation markers (ki67 and proliferating cell nuclear antigen [PCNA]) and α-SMA were frequently observed in the vicinity of the root canal orifice 7 d after treatment, which is the early stage of healing. By contrast, in mature teeth, the number of CD73-, CD90-, and CD146-immunopositive cells increased at the apical site after 7 and 28 d. CD90- and CD146-immunopositive cells expressed cell proliferation markers (ki67 or PCNA) after 7 d. MSC migration after BC-REP likely varies based on tooth maturity, resulting in different healing phenotypes.

    DOI： 10.1177/00220345251325826

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    Other Link： https://journals.sagepub.com/doi/full-xml/10.1177/00220345251325826

  • An Evaluation of the Biocompatibility and Chemical Properties of Two Bioceramic Root Canal Sealers in a Sealer Extrusion Model of Rat Molars Reviewed

    Shintaro Takahara, Naoki Edanami, Razi Saifullah Ibn Belal, Kunihiko Yoshiba, Shoji Takenaka, Naoto Ohkura, Nagako Yoshiba, Susan Gomez-Kasimoto, Yuichiro Noiri

    Journal of Functional Biomaterials   16 ( 1 )   14 - 14   2025.1

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    Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

    This study assessed the biocompatibility and chemical properties of two bioceramic root canal sealers, EndoSequence BC Sealer (EBC) and Nishika Canal Sealer BG (NBG), using a sealer extrusion model. Eight-week-old male Wistar rats were used. The mesial root canals of the upper first molars were pulpectomized and overfilled with EBC, NBG, or, as reference, epoxy resin-based AH Plus (AHP). After 28 days, periapical tissue reactions were assessed using microcomputed tomography and histological staining. The elemental composition and chemical composition of the extruded EBC and NBG were analyzed at Day 1 and 28 using an electron probe microanalyzer and micro-Raman spectroscopy. No periapical lesions were observed with the sealer extrusion. Additionally, inflammation around the extruded EBC and NBG was minimal to mild on Day 28, whereas moderate inflammation was found around the extruded AHP. Silicon concentration in the extruded EBC and NBG decreased significantly from Day 1 to 28, with almost no silicon present on Day 28. Furthermore, the extruded EBC and NBG became calcium- and phosphorus-rich, showing a Raman band for hydroxyapatite on Day 28. In conclusion, EBC and NBG demonstrated favorable biocompatibility and the ability to release silicon elements and produce hydroxyapatite when extruded into the periapical tissues. AHP showed moderate periapical tissue irritancy.

    DOI： 10.3390/jfb16010014

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  • Polycomb protein Bmi1 promotes odontoblast differentiation by accelerating Wnt and BMP signaling pathways. International journal

    Akihiro Hosoya, Hiroaki Takebe, Yuri Seki-Kishimoto, Yukiko Noguchi, Tadashi Ninomiya, Akira Yukita, Nagako Yoshiba, Ayako Washio, Masahiro Iijima, Takahiko Morotomi, Chiaki Kitamura, Hiroaki Nakamura

    Histochemistry and cell biology   163 ( 1 )   11 - 11   2024.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    Bmi1 is a polycomb protein localized in stem cells and maintains their stemness. This protein is also reported to regulate the expression of various differentiation genes. In this study, to analyze the role of Bmi1 during dentinogenesis, we examined the immunohistochemical localization of Bmi1 during rat tooth development as well as after cavity preparation. Bmi1 localization was hardly detected in the dental mesenchyme at the bud and cap stages. After the bell stage, however, this protein became detectable in preodontoblasts and early odontoblasts just beginning dentin matrix secretion. As dentin formation progressed, Bmi1 immunoreactivity in the odontoblasts decreased in intensity. After cavity preparation, cells lining the dentin and some pulp cells under the cavity were immunopositive for Bmi1 at 4 days. Odontoblast-like cells forming reparative dentin were immunopositive for Bmi1 at 1 week, whereas their immunoreactivity was not detected after 8 weeks. We further analyzed the function of Bmi1 using KN-3 cells, a dental mesenchymal cell line. Overexpression of Bmi1 in KN-3 cells promoted mineralized tissue formation. In contrast, siRNA knockdown of Bmi1 in KN-3 cells reduced alkaline phosphatase activity and the expression of odontoblast differentiation marker genes such as Runx2, osterix, and osteocalcin. Additionally, KN-3 cells transfected with siRNA against Bmi1 showed reduced nuclear transition of β-catenin and expression of phosphorylated-Smad1/5/8. Taken together, these findings suggest that Bmi1 was localized in the odontoblast-lineage cells in their early differentiation stages. Bmi1 might positively regulate their differentiation by accelerating Wnt and BMP signaling pathways.

    DOI： 10.1007/s00418-024-02337-2

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  • 各種受容細胞におけるP.gingivalis由来外膜小胞の取り込み動態解析

    大倉 直人, 吉羽 永子, 立川 正憲, 中馬 吉郎, Baldeon Gutierrez Rosa Edith, 高原 信太郎, Gomez Kasimoto Susan, 井田 貴子, 枝並 直樹, 竹中 彰治, 野杁 由一郎

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   161回   150 - 150   2024.11

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    Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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  • Development and Characterization of a Three-Dimensional Organotypic In Vitro Oral Cancer Model with Four Co-Cultured Cell Types, Including Patient-Derived Cancer-Associated Fibroblasts. International journal

    Yuka Aizawa, Kenta Haga, Nagako Yoshiba, Witsanu Yortchan, Sho Takada, Rintaro Tanaka, Eriko Naito, Tatsuya Abé, Satoshi Maruyama, Manabu Yamazaki, Jun-Ichi Tanuma, Kazuyo Igawa, Kei Tomihara, Shinsaku Togo, Kenji Izumi

    Biomedicines   12 ( 10 )   2024.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    Background/Objectives: Cancer organoids have emerged as a valuable tool of three-dimensional (3D) cell cultures to investigate tumor heterogeneity and predict tumor behavior and treatment response. We developed a 3D organotypic culture model of oral squamous cell carcinoma (OSCC) to recapitulate the tumor-stromal interface by co-culturing four cell types, including patient-derived cancer-associated fibroblasts (PD-CAFs). Methods: A stainless-steel ring was used twice to create the horizontal positioning of the cancer stroma (adjoining normal oral mucosa connective tissue) and the OSCC layer (surrounding normal oral mucosa epithelial layer). Combined with a structured bi-layered model of the epithelial component and the underlying stroma, this protocol enabled us to construct four distinct portions mimicking the oral cancer tissue arising in the oral mucosa. Results: In this model, α-smooth muscle actin-positive PD-CAFs were localized in close proximity to the OSCC layer, suggesting a crosstalk between them. Furthermore, a linear laminin-γ2 expression was lacking at the interface between the OSCC layer and the underlying stromal layer, indicating the loss of the basement membrane-like structure. Conclusions: Since the specific 3D architecture and polarity mimicking oral cancer in vivo provides a more accurate milieu of the tumor microenvironment (TME), it could be crucial in elucidating oral cancer TME.

    DOI： 10.3390/biomedicines12102373

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  • 歯髄創傷治癒および歯髄再生過程におけるリン酸トランスポーター(Pit-1)の免疫組織学的解析

    大倉 直人, Baldeon Gutierrez Rosa Edith, 高原 信太郎, Gomez Kasimoto Susan Kiara, 枝並 直樹, 井田 貴子, 外園 真規, 永田 量子, 竹中 彰治, 吉羽 邦彦, 吉羽 永子, 野杁 由一郎

    日本歯科保存学雑誌   67 ( 3 )   165 - 173   2024.6

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    Language：Japanese   Publisher：(NPO)日本歯科保存学会  

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  • A novel macrolide–Del-1 axis to regenerate bone in old age Reviewed

    Kridtapat Sirisereephap, Hikaru Tamura, Jong-Hyung Lim, Meircurius Dwi Condro Surboyo, Toshihito Isono, Takumi Hiyoshi, Andrea L. Rosenkranz, Yurie Sato-Yamada, Hisanori Domon, Akari Ikeda, Tomoyasu Hirose, Toshiaki Sunazuka, Nagako Yoshiba, Hiroyuki Okada, Yutaka Terao, Takeyasu Maeda, Koichi Tabeta, Triantafyllos Chavakis, George Hajishengallis, Tomoki Maekawa

    iScience   27 ( 2 )   108798 - 108798   2024.2

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.isci.2024.108798

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  • Wound-healing Processes After Pulpotomy in the Pulp Tissue of Type 1 Diabetes Mellitus Model Rats Reviewed

    Rosa Baldeon-Gutierrez, Naoto Ohkura, Kunihiko Yoshiba, Nagako Yoshiba, Aiko Tohma, Ryosuke Takeuchi, Razi Saifullah Ibn Belal, Naoki Edanami, Shintaro Takahara, Susan Gomez-Kasimoto, Takako Ida, Yuichiro Noiri

    Journal of Endodontics   50 ( 2 )   196 - 204   2024.2

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.joen.2023.10.016

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  • In Vivo assessment of the Apatite-Forming Ability of New-Generation Hydraulic Calcium Silicate Cements Using a Rat Subcutaneous Implantation Model Reviewed International journal

    Naoki Edanami, Shouji Takenaka, Razi Saifullah, Ibn Belal, Kunihiko Yoshiba, Shintaro Takahara, Nagako Yoshiba, Naoto Ohkura, Yuichiro Noiri

    Journal of Functional Biomaterials   14 ( 4 )   2023.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    Hydroxyapatite formation on endodontic hydraulic calcium silicate cements (HCSCs) plays a significant role in sealing the root canal system and elevating the hard-tissue inductivity of the materials. This study evaluated the in vivo apatite-forming ability of 13 new-generation HCSCs using an original HCSC (white ProRoot MTA: PR) as a positive control. The HCSCs were loaded into polytetrafluoroethylene tubes and implanted in the subcutaneous tissue of 4-week-old male Wistar rats. At 28 days after implantation, hydroxyapatite formation on the HCSC implants was assessed with micro-Raman spectroscopy, surface ultrastructural and elemental characterization, and elemental mapping of the material-tissue interface. Seven new-generation HCSCs and PR had a Raman band for hydroxyapatite (v1 PO43- band at 960 cm-1) and hydroxyapatite-like calcium-phosphorus-rich spherical precipitates on the surfaces. The other six HCSCs with neither the hydroxyapatite Raman band nor hydroxyapatite-like spherical precipitates did not show calcium-phosphorus-rich hydroxyapatite-layer-like regions in the elemental mapping. These results indicated that 6 of the 13 new-generation HCSCs possessed little or no ability to produce hydroxyapatite in vivo, unlike PR. The weak in vivo apatite-forming ability of the six HCSCs may have a negative impact on their clinical performance.

    DOI： 10.3390/jfb14040213

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  • In Vivo Assessment of the Calcium Salt-Forming Ability of a New Calcium Silicate-Based Intracanal Medicament: Bio-C Temp. Reviewed International journal

    Naoki Edanami, Razi Saifullah Ibn Belal, Shoji Takenaka, Kunihiko Yoshiba, Rosa Edith Baldeon Gutierrez, Shintaro Takahara, Nagako Yoshiba, Naoto Ohkura, Yuichiro Noiri

    Dentistry journal   11 ( 4 )   2023.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    Calcium salt precipitation induced by intracanal medicaments contributes to the formation of apical hard tissue during apexification. This study compared the calcium salt-forming ability of a new calcium silicate-based intracanal medicament (Bio-C Temp) with that of two commercial calcium hydroxide pastes (Calcipex Plane II and Vitapex) in a rat subcutaneous implantation model. Polytetrafluoroethylene tubes containing each of the three materials were subcutaneously implanted in 4-week-old male Wistar rats. After 28 days, the composition and amount of calcium salts formed at the material-tissue interface were assessed using micro-Raman spectroscopy, X-ray diffraction, and elemental mapping. The tested materials produced white precipitates that had Raman spectra with peaks corresponding to hydroxyapatite and calcite. X-ray diffraction detected hydroxyapatite formation on Calcipex Plane II and Vitapex implants, as well as calcite formation on all three materials. Elemental mapping revealed that Bio-C Temp generated significantly smaller calcium- and phosphorus-rich calcified regions within the subcutaneous connective tissue than Vitapex. These results indicate that Bio-C Temp produced less calcium salt in rat subcutaneous tissue than Vitapex, although all materials formed hydroxyapatite and calcite in rat subcutaneous tissue. Bio-C Temp could be less effective than Vitapex in promoting apical hard tissue formation during apexification.

    DOI： 10.3390/dj11040091

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  • Prostaglandin E2-Transporting Pathway and Its Roles via EP2/EP4 in Cultured Human Dental Pulp. Reviewed International journal

    Naoto Ohkura, Kunihiko Yoshiba, Nagako Yoshiba, Yohei Oda, Naoki Edanami, Hayato Ohshima, Shoji Takenaka, Takashi Okiji, Yuichiro Noiri

    Journal of endodontics   49 ( 4 )   Ahead of online - 418   2023.2

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    INTRODUCTION: Prostaglandin E2 (PGE2) exerts biological actions through its transport pathway involving intracellular synthesis, extracellular transport, and receptor binding. This study aimed to determine the localization of the components of the PGE2-transporting pathway in human dental pulp and explore the relevance of PGE2 receptors (EP2/EP4) to angiogenesis and dentinogenesis. METHODS: Protein localization of microsomal PGE2 synthase (mPGES), PGE2 transporters [(multidrug resistance-associated protein-4 (MRP4) and prostaglandin transporter (PGT)], and EP2/EP4 was analyzed using double immunofluorescence staining. Tooth slices from human third molars were cultured with or without butaprost (EP2 agonist) or rivenprost (EP4 agonist) for 1 week. Morphometric analysis of endothelial cell filopodia was performed to evaluate angiogenesis, and real-time polymerase chain reaction was performed to evaluate angiogenesis and odontoblast differentiation markers. RESULTS: MRP4 and PGT were colocalized with mPGES and EP2/EP4 in odontoblasts and endothelial cells. Furthermore, MRP4 was colocalized with mPGES and EP4 in human leukocyte antigen-DR-expressing dendritic cells. In the tooth slice culture, EP2/EP4 agonists induced significant increases in the number and length of filopodia and mRNA expression of angiogenesis markers (vascular endothelial growth factor and fibroblast growth factor-2) and odontoblast differentiation markers (dentin sialophosphoprotein and collagen type 1). CONCLUSIONS: PGE2-producing enzyme (mPGES), transporters (MRP4 and PGT), and PGE2-specific receptors (EP2/EP4) were immunolocalized in various cellular components of the human dental pulp. EP2/EP4 agonists promoted endothelial cell filopodia generation and upregulated angiogenesis- and odontoblast differentiation-related genes, suggesting that PGE2 binding to EP2/EP4 is associated with angiogenic and dentinogenic responses.

    DOI： 10.1016/j.joen.2023.01.009

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  • SVCT2-GLUT1-mediated ascorbic acid transport pathway in rat dental pulp and its effects during wound healing. Reviewed International journal

    Naoto Ohkura, Kunihiko Yoshiba, Nagako Yoshiba, Naoki Edanami, Hayato Ohshima, Shoji Takenaka, Yuichiro Noiri

    Scientific reports   13 ( 1 )   1251 - 1251   2023.1

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    Ascorbic acid (AA; vitamin C) plays a crucial role in the biosynthesis and secretion of collagen to produce the organic matrix of hard tissues. Nevertheless, the detailed mechanism by which AA induces reparative dentinogenesis is still unknown. This study aimed to investigate the pathway and function of AA during wound healing in a rat pulpotomy model. Sodium-dependent vitamin C transporter (SVCT) 2 and glucose transporter (GLUT) 1 were detected in odontoblasts, endothelial cells, and nerve fibers in normal pulp tissues. SVCT2 and GLUT1 were also expressed in odontoblast-like cells in pulpotomized tissues of Wistar rats, and immunopositive cells of SVCT2 were significantly increased at 5 days after pulpotomy (p < 0.05). By contrast, osteogenic disorder Shionogi (ODS) rats, which cannot generate AA, also expressed SVCT2 and GLUT1 in normal and wound healing conditions. However, in ODS rats, when compared with the AA-addition group, the formation of dentin bridges in the AA-loss group was not evident, a layer of osteopontin was significantly increased beneath the wound surface (p < 0.05), and alpha smooth muscle actin at the odontoblast-like cells observed along this layer was significantly increased (p < 0.05), but not Nestin. Moreover, the amounts of type 1 collagen generated in the reparative dentin and beneath the wound healing site were significantly diminished (p < 0.05). Macrophages expressing CD68 and CD206 increased beneath the wound site. Hence, AA may be involved in odontoblast-like cell differentiation and anti-inflammatory response during dental pulp wound healing. Our results provide new insights into the function of AA through SVCT2 and GLUT1 in reparative dentinogenesis and may help in developing new therapeutic targets for dental pulpal disease.

    DOI： 10.1038/s41598-023-28197-9

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  • Gli1+-PDL Cells Contribute to Alveolar Bone Homeostasis and Regeneration. Reviewed International journal

    N Shalehin, Y Seki, H Takebe, S Fujii, T Mizoguchi, H Nakamura, N Yoshiba, K Yoshiba, M Iijima, T Shimo, K Irie, A Hosoya

    Journal of dental research   220345221106921 - 220345221106921   2022.7

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    The periodontal ligament (PDL) contains mesenchymal stem cells (MSCs) that can differentiate into osteoblasts, cementoblasts, and fibroblasts. Nevertheless, the distribution and characteristics of these cells remain uncertain. Gli1, an essential hedgehog signaling transcription factor, functions in undifferentiated cells during embryogenesis. Therefore, in the present study, the differentiation ability of Gli1+ cells was examined using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. In 4-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were only slightly detected in the PDL, around endomucin-expressing blood vessels. These cells had proliferated over time, localizing in the PDL as well as on the bone and cementum surfaces at day 28. However, in 8-wk-old iGli1/Tomato mice, Gli1/Tomato+ cells were quiescent, as most cells were not immunoreactive for Ki-67. These cells in 8-wk-old mice exhibited high colony-forming unit fibroblast activity and were capable of osteogenic, chondrogenic, and adipogenic differentiation in vitro. In addition, after transplantation of teeth of iGli1/Tomato mice into the hypodermis of wild-type mice, Tomato fluorescence indicating the progeny of Gli1+ cells was detected in the osteoblasts and osteocytes of the regenerated bone. These results demonstrate that Gli1+ cells in the PDL were MSCs and could contribute to the alveolar bone regeneration.

    DOI： 10.1177/00220345221106921

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  • Laminin Isoforms in Human Dental Pulp: Lymphatic Vessels Express Laminin-332 and Schwann Cell-Associated Laminin-211 Modulates CD163 Expression of M2-Like Macrophages Reviewed International journal

    Nagako Yoshiba, Naoki Edanami, Naoto Ohkura, Tomoki Maekawa, Naoki Takahashi, Takahiro Tsuzuno, Takeyasu Maeda, Koichi Tabeta, Kenji Izumi, Yuichiro Noiri, Kunihiko Yoshiba

    ImmunoHorizons   5 ( 12 )   1008 - 1020   2021.12

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    Laminin, a basement membrane heterotrimeric glycoprotein composed of α/β/γ subunits, has important tissue-specific functions in the control of cellular behavior. Our recent study showed the colocalization of CD163+ M2-like macrophages with Schwann cells in human dental pulp, leading us to hypothesize that the laminin isoform of Schwann cells is associated with CD163 expression. The present study investigated the distribution of laminin isoforms in human dental pulp and the underlying mechanisms that affect macrophage phenotypes. Immunofluorescence analysis indicated that blood vessels were exclusively positive for laminin α4 and α5, whereas laminin α2 was associated with Schwann cells. Unexpectedly, laminin α3/laminin-332 (α3β3γ2) was detected on lymphatic vessels. In intact and carious teeth, CD163+ cells were associated with laminin α2, whereas CD206 single-positive cells were present inside, outside, and along blood vessels. In vitro incubation of THP-1 macrophages in plates coated with laminin-211/511 or its functionally analogous E8 fragments of α-chain (E8-α) indicated that cell shapes differed between macrophages grown on laminin-211/E8-α2 and macrophages grown on laminin-511/E8-α5. Laminin-211/E8-α2-coated plates upregulated CD163 expression, compared with laminin-511/E8-α5-coated plates. Integrin α3- and integrin α6-neutralizing Abs altered the shape of THP-1 macrophages and upregulated mRNA levels of CD206 and CD163 in macrophages grown on laminin-511; the neutralizing Abs did not affect macrophages grown on laminin-211. These findings suggest that laminin isoforms differentially regulate macrophage behavior via distinct integrin-laminin affinities. Of note, laminin-332 is expressed by pulpal lymphatic vessels, the existence of which has been debated; laminin-211 might have a role in maintaining CD163 expression on macrophages.

    DOI： 10.4049/immunohorizons.2100110

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  • Effect of a resin-modified calcium silicate cement on inflammatory cell infiltration and reparative dentin formation after pulpotomy in rat molars. Reviewed International journal

    Naoki Edanami, Razi Saifullah Ibn Belal, Kunihiko Yoshiba, Nagako Yoshiba, Naoto Ohkura, Shoji Takenaka, Yuichiro Noiri

    Australian endodontic journal : the journal of the Australian Society of Endodontology Inc   48 ( 2 )   297 - 304   2021.10

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    Language：English   Publishing type：Research paper (scientific journal)  

    Resin monomers and polymerisation initiators have been shown to be cytotoxic for pulp cells and to disturb odontoblast differentiation. This study aimed to compare the effect of a resin-modified calcium silicate cement (TheraCal LC; TC) and a resin-free calcium silicate cement (ProRoot MTA; PR) on pulpal healing after pulpotomy. Pulpotomy was performed on the maxillary first molars of 8-week-old rats using either PR or TC. After 1, 3, 7, 14 and 28 days, pulpal responses were assessed by micro-computed tomography, haematoxylin-eosin staining and immunostaining against CD68, which is a pan-macrophage marker. The results showed that pulpotomy with TC induced persistent infiltration of inflammatory cells, including CD68-positive macrophages, and delayed the formation of reparative dentin as compared with that with PR, although both materials allowed pulpal healing over the long term. Therefore, resin-modified TC was not as biocompatible nor bioinductive as resin-free PR when applied on the healthy pulp of rat molars.

    DOI： 10.1111/aej.12568

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  • Apatite-Forming Ability of Flowable vs. Putty Formulations of Newly Developed Bioactive Glass-Containing Endodontic Cement Reviewed

    Naoki Edanami, Razi Saifullah Ibn Belal, Shoji Takenaka, Kunihiko Yoshiba, Nagako Yoshiba, Naoto Ohkura, Shintaro Takahara, Yuichiro Noiri

    Applied Sciences   11 ( 19 )   8969 - 8969   2021.9

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    This study compared the apatite-forming ability (AFA) levels of flowable and putty formulations of Nishika Canal Sealer BG Multi (F-NBG and P-NBG, respectively) and attempted to clarify the cause of differences in the AFA levels of F-NBG and P-NBG. NBG samples were aged in simulated body fluid (SBF) or 1-, 5-, or 10-g/L bovine serum albumin-containing SBF (BSA-SBF) and analyzed in terms of their ultrastructures, elemental compositions, and Raman spectra to identify apatite formation. The phosphate ion consumption rates of NBG samples in the media were evaluated as an indicator of apatite growth. The original elemental composition, calcium ion release, and alkalizing ability levels of F-NBG and P-NBG were also evaluated. Apparent apatite formation was detected on all NBG samples except F-NBG aged in 10-g/L BSA-SBF. P-NBG consumed phosphate ions faster than F-NBG. As-prepared P-NBG showed more silicon elements on its surface than as-prepared F-NBG. P-NBG released more calcium ions than F-NBG, although their alkalizing ability levels did not differ statistically. In conclusion, the AFA of P-NBG was greater than that of F-NBG, probably because of the greater ability of P-NBG to expose silanol groups on the surface and release calcium ions.

    DOI： 10.3390/app11198969

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  • Comparison of calcium and hydroxyl ion release ability and in vivo apatite-forming ability of three bioceramic-containing root canal sealers. Reviewed International journal

    Razi Saifullah Ibn Belal, Naoki Edanami, Kunihiko Yoshiba, Nagako Yoshiba, Naoto Ohkura, Shoji Takenaka, Yuichiro Noiri

    Clinical oral investigations   26 ( 2 )   1443 - 1451   2021.8

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    OBJECTIVE: Bioceramic-containing root canal sealers promote periapical healing via Ca2+ and OH- release and apatite formation on the surface. This study aimed to compare Ca2+ and OH- release and in vivo apatite formation of three bioceramic-containing root canal sealers: EndoSequence BC sealer (Endo-BC), MTA Fillapex (MTA-F), and Nishika Canal Sealer BG (N-BG). MATERIALS AND METHODS: Polytetrafluoroethylene tubes filled with sealers were immersed in distilled water for 6 and 12 h and for 1, 7, 14, and 28 days to measure Ca2+ and OH- release. Additionally, tubes filled with sealers were implanted in the backs of rats for 28 days, and in vivo apatite formation was analyzed using an electron probe microanalyzer. RESULTS: Endo-BC released significantly more Ca2+ than the other sealers at 6 and 12 h and 1 day. Ca2+ release was significantly lower from N-BG than from Endo-BC and MTA-F at 14 and 28 days. OH- release was significantly higher from Endo-BC than from the other sealers throughout the experiment, except at 1 day. OH- release was lower from N-BG than from MTA-F at 6 h and 7 days. Only Endo-BC implants exhibited apatite-like calcium-, phosphorus-, oxygen-, and carbon-rich spherulites and apatite layer-like calcium- and phosphorus-rich, but radiopaque element-free, surface regions. CONCLUSIONS: Ca2+ and OH- release is ranked as follows: Endo-BC > MTA-F > N-BG. Only Endo-BC demonstrated in vivo apatite formation. CLINICAL RELEVANCE: Endo-BC could promote faster periapical healing than MTA-F and N-BG.

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  • Impact of remnant healthy pulp and apical tissue on outcomes after simulated regenerative endodontic procedure in rat molars. Reviewed International journal

    Naoki Edanami, Kunihiko Yoshiba, Mari Shirakashi, Razi Saifullah Ibn Belal, Nagako Yoshiba, Naoto Ohkura, Aiko Tohma, Ryosuke Takeuchi, Takashi Okiji, Yuichiro Noiri

    Scientific reports   10 ( 1 )   20967 - 20967   2020.12

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    When regenerative endodontic procedures (REPs) are performed on immature teeth diagnosed with pulp necrosis and apical periodontitis, various healing patterns occur. Furthermore, infected immature teeth with endodontic disorders often exhibit some remnant pulp and apical tissue. Therefore, this study investigated the impact of remnant healthy or fully functional pulp and apical tissue on healing patterns after REPs. Simulated REPs were performed on non-infected immature rat molars with different amounts of remnant pulp and apical tissue. Healing patterns in these teeth were assessed after 28 days. Teeth with 0.81-0.91 mm of remnant pulp healed with pulp-like tissue, dentin, and osteodentin-like dentin-associated mineralized tissue (OSD-DAMT); teeth with 0.60-0.63 mm of remnant pulp healed with pulp-like tissue and OSD-DAMT; teeth with 0.13-0.43 mm of remnant pulp healed with periodontal ligament (PDL)-like tissue, OSD-DAMT, and cementum-like dentin-associated mineralized tissue (CEM-DAMT); and teeth with disorganization of pulp and apical tissues at 0.15-0.38 mm beyond the root apex healed with PDL-like tissue, CEM-DAMT, and intracanal bone (IB). Loss of Hertwig's epithelial root sheath was observed with IB formation. These results showed that four distinct healing patterns occurred after REPs, depending on the preoperative amount of remnant healthy pulp and apical tissue.

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  • M2 Phenotype Macrophages Colocalize with Schwann Cells in Human Dental Pulp. Reviewed International journal

    Yoshiba N, Edanami N, Ohkura N, Maekawa T, Takahashi N, Tohma A, Izumi K, Maeda T, Hosoya A, Nakamura H, Tabeta K, Noiri Y, Yoshiba K.

    Journal of Dental Research   99 ( 3 )   329 - 338   2020.3

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    Macrophages are immune cells with high plasticity that perform many functions related to tissue injury and repair. They are generally categorized as 2 functional phenotypes: M1 (proinflammatory) and M2 (anti-inflammatory and prohealing). To investigate the role of macrophages in human dental pulp, we examined the localization and distributional alterations of macrophages in healthy dental pulp as well as during the reparative process of pulp capping with mineral trioxide aggregate (MTA) and in cariously inflamed pulp of adult human teeth. We also quantified the populations of M1/M2 macrophages in healthy dental pulp by flow cytometric analysis. CD68+CD86+ cells (M1 phenotype) and CD68+CD163+ cells (M2 phenotype) were 2.11% ± 0.50% and 44.99% ± 2.22%, respectively, of 2.96% ± 0.41% CD68+ cells (pan-macrophages) in whole healthy dental pulp. Interestingly, M2 phenotype macrophages were associated with Schwann cells in healthy pulp, during mineralized bridge formation, and in pulp with carious infections in vivo. Furthermore, the M2 macrophages associated with Schwann cells expressed brain-derived neurotrophic factor (BDNF) under all in vivo conditions. Moreover, we found that plasma cells expressed BDNF. Coculture of Schwann cells isolated from human dental pulp and human monocytic cell line THP-1 showed that Schwann cells induced M2 phenotypic polarization of THP-1 cell-derived macrophages. The THP-1 macrophages that maintained contact with Schwann cells were stimulated, leading to elongation of their cell shape and expression of M2 phenotype marker CD163 in cocultures. In summary, we revealed the spatiotemporal localization of macrophages and potent induction of the M2 phenotype by Schwann cells in human dental pulp. M2 macrophages protect neural elements, whereas M1 cells promote neuronal destruction. Therefore, suppressing the neurodestructive M1 phenotype and maintaining the neuroprotective M2 phenotype of macrophages by Schwann cells may be critical for development of effective treatment strategies to maintain the viability of highly innervated dental pulp.

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  • Immunohistochemistry and gene expression of GLUT1, RUNX2 and MTOR in reparative dentinogenesis. Reviewed International journal

    Ryosuke Takeuchi, Naoto Ohkura, Kunihiko Yoshiba, Aiko Tohma, Nagako Yoshiba, Naoki Edanami, Mari Shirakashi, Razi Saifullah Ibn Belal, Hayato Ohshima, Yuichiro Noiri

    Oral diseases   26 ( 2 )   341 - 349   2020.3

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    OBJECTIVES: To determine glucose transporter 1 (GLUT1) and runt-related transcription factor 2 (RUNX2) expression during reparative dentinogenesis after pulpotomy with mineral trioxide aggregate (MTA) capping. SUBJECTS AND METHODS: Eight-week-old male Wistar rats were used. Pulp of the upper left first molar was exposed and capped with MTA. The upper right first molar of the same animal was used as a control. After collecting molars at various time points, GLUT1, RUNX2 and mammalian target of rapamycin (MTOR) were examined by immunohistochemistry. mRNA levels of Slc2a1 (encoding GLUT1), Runx2, Nestin and Mtor were determined by real-time PCR. RESULTS: Pulp exhibited progressive formation of reparative dentine lined with GLUT1- and MTOR-immunoreactive odontoblast-like cells at 5 days after pulpotomy. RUNX2 was detected in nuclei of most pulp tissue cells at day 5 after pulpotomy. Double immunofluorescence staining revealed GLUT1 immunoreactivity on odontoblast-like cells positive for Nestin or RUNX2, 5 days after pulpotomy. Slc2a1, Runx2, Nestin and Mtor mRNA levels were significantly upregulated on days 3-5 after pulpotomy. CONCLUSIONS: After rat molar pulpotomy, dental pulp induced formation of reparative dentine with colocalization of GLUT1 and Nestin or RUNX2. Moreover, mRNA levels of Slc2a1, Runx2, Nestin and Mtor were significantly upregulated in pulpotomized dental pulp.

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  • Glucose Transporter 2 and 4 Are Involved in Glucose Supply during Pulpal Wound Healing after Pulpotomy with Mineral Trioxide Aggregate in Rat Molars. Reviewed International journal

    Aiko Tohma, Naoto Ohkura, Kunihiko Yoshiba, Ryosuke Takeuchi, Nagako Yoshiba, Naoki Edanami, Mari Shirakashi, Razi Saifullah Ibn Belal, Hayato Ohshima, Yuichiro Noiri

    Journal of endodontics   46 ( 1 )   81 - 88   2020.1

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    INTRODUCTION: Pulp capping materials allow healing of injured pulp with a layer of reparative dentin. Glucose is needed to cure the injured area. Glucose is transported by glucose transporter (Glut) 2 and Glut4, which are transmembrane proteins that act as gatekeepers. We hypothesized that the transport of glucose via Glut2/Glut4 might contribute to the production of a dentin bridge during wound healing. Therefore, we explored Glut2 and Glut4 expression during reparative dentinogenesis after mineral trioxide aggregate capping. METHODS: The upper left first molar of 8-week-old Wistar rats underwent pulpotomy with mineral trioxide aggregate. At 1, 3, 5, 7, and 14 days after treatment, localization and colocalization of Glut2, Glut4, nestin (odontoblast marker), and antiendothelial cell antigen 1 (RECA-1; endothelial cell marker) were analyzed with immunohistochemical staining. Messenger RNA expression levels of Slc2a2 (encoding Glut2), Slc2a4 (encoding Glut4), Igf-1r (encoding insulinlike growth factor 1 receptor), and nestin were analyzed in the extracted teeth using real-time polymerase chain reaction. RESULTS: Glut2 and Glut4 were localized within odontoblasts and endothelial cells in normal control teeth. Three days after pulpotomy, Glut2- and Glut4-positive cells were detected; 7 days after pulpotomy, immunoreactivity for Glut2 and Glut4 was confined to newly differentiated odontoblastlike cells arranged beneath reparative dentin. Messenger RNA expression levels of Slc2a2 and Slc2a4 were significantly up-regulated after pulpotomy. CONCLUSIONS: Glut2 and Glut4 regulate glucose transport during wound healing beneath the injured area. This may contribute to the development of new vital pulp therapy for patients with deep caries.

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  • Detection of bone marrow-derived fibrocytes in human dental pulp repair. Reviewed International journal

    N Yoshiba, N Edanami, A Tohma, R Takeuchi, N Ohkura, A Hosoya, Y Noiri, H Nakamura, K Yoshiba

    International endodontic journal   51 ( 11 )   1187 - 1195   2018.11

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    AIM: To explore the expression profile of CD45+/pro-collagen I+ fibrocytes in intact dental pulps as well as during wound healing in adult dental pulp tissue. METHODOLOGY: A total of 16 healthy permanent teeth were obtained from young patients (18 to 25 years) undergoing orthodontic treatment. Routine pulp capping with mineral trioxide aggregate (MTA) was performed under local anaesthesia to induce a mineralized barrier at the exposed surface. Teeth were extracted from patients after 7, 14 and 35 days. Sections of the extracted teeth were prepared and stained for various markers using indirect immunofluorescence. Fibrocytes were counted, and the data were statistically evaluated using the Dunnett test. RESULTS: In uninflammed pulp tissue, a pro-collagen I-positive reaction was detected in odontoblasts, as well as in perivascular cells. Most of the CD45-positive cells were negative for pro-collagen I in normal pulp tissue, whereas CD45+/pro-collagen I+ fibrocytes were detected 7 days after injury. At day 14, fibrocytes were recognized under the fibrous matrix in contact with MTA and had infiltrated into regions of new capillary formation, where the fibrocytes were positively stained for vascular endothelial growth factor. By 35 days, fibrocytes were few, coincident with the formation of dentine bridges. The number of fibrocytes peaked 7 days post-injury and decreased at 14 days. CONCLUSIONS: The presence of fibrocytes in human pulp wound healing was observed. The spatiotemporal distribution of fibrocytes suggests that fibrocytes are involved in the early stages of pulp wound healing, specifically by contributing to new blood vessel formation.

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  • Orthodontic force application upregulated pain-associated prostaglandin-I2/PGI2-receptor/TRPV1 pathway-related gene expression in rat molars. Reviewed

    Mariko Ohkura, Naoto Ohkura, Nagako Yoshiba, Kunihiko Yoshiba, Hiroko Ida-Yonemochi, Hayato Ohshima, Isao Saito, Takashi Okiji

    Odontology   106 ( 1 )   2 - 10   2018.1

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    DOI： 10.1007/s10266-017-0309-2

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  • Bioactivity and biomineralization ability of calcium silicate-based pulp-capping materials after subcutaneous implantation Reviewed

    G. Hinata, K. Yoshiba, L. Han, N. Edanami, N. Yoshiba, T. Okiji

    INTERNATIONAL ENDODONTIC JOURNAL   50   E40 - E51   2017.12

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    DOI： 10.1111/iej.12802

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  • Effects of pulpotomy using mineral trioxide aggregate on prostaglandin transporter and receptors in rat molars. Reviewed International journal

    Naoto Ohkura, Naoki Edanami, Ryosuke Takeuchi, Aiko Tohma, Mariko Ohkura, Nagako Yoshiba, Kunihiko Yoshiba, Hiroko Ida-Yonemochi, Hayato Ohshima, Takashi Okiji, Yuichiro Noiri

    Scientific reports   7 ( 1 )   6870 - 6870   2017.7

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    DOI： 10.1038/s41598-017-07167-y

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  • Characterization of Dental Pulp Myofibroblasts in Rat Molars after Pulpotomy Reviewed

    Naoki Edanami, Nagako Yoshiba, Naoto Ohkura, Ryosuke Takeuchi, Aiko Tohma, Yuichiro Noiri, Kunihiko Yoshiba

    JOURNAL OF ENDODONTICS   43 ( 7 )   1116 - 1121   2017.7

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    DOI： 10.1016/j.joen.2017.02.018

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  • 象牙芽細胞分化におけるポリコーム群タンパク質Bmi1の機能

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 鷲尾 絢子, 諸冨 孝彦, 北村 知昭, 山本 昭夫, 中村 浩彰

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   145回   43 - 43   2016.10

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  • GaAlAs laser-induced pulp mineralization involves dentin matrix protein 1 and osteopontin expression Reviewed

    Y. Shigetani, N. Ohkura, K. Yoshiba, H. Ohshima, A. Hosoya, N. Yoshiba, T. Okiji

    ORAL DISEASES   22 ( 5 )   399 - 405   2016.7

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  • Correlation between Fibrillin-1 Degradation and mRNA Downregulation and Myofibroblast Differentiation in Cultured Human Dental Pulp Tissue Reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Erika Takei, Naoki Edanami, Youhei Oda, Akihiro Hosoya, Hiroaki Nakamura, Takashi Okiji

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   63 ( 6 )   438 - 448   2015.6

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  • Temporospatial localization of dentine matrix protein 1 following direct pulp capping with calcium hydroxide in rat molars Reviewed

    Y. Shigetani, K. Yoshiba, M. Kuratate, E. Takei, N. Yoshiba, Y. Yamanaka, H. Ohshima, T. Okiji

    INTERNATIONAL ENDODONTIC JOURNAL   48 ( 6 )   573 - 581   2015.6

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  • Initial Transient Accumulation of M2 Macrophage-associated Molecule-expressing Cells after Pulpotomy with Mineral Trioxide Aggregate in Rat Molars Reviewed

    Erika Takei, Yoshimi Shigetani, Kunihiko Yoshiba, Go Hinata, Nagako Yoshiba, Takashi Okiji

    JOURNAL OF ENDODONTICS   40 ( 12 )   1983 - 1988   2014.12

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    DOI： 10.1016/j.joen.2014.08.012

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  • Prostaglandin Transporting Protein-mediated Prostaglandin E-2 Transport in Lipopolysaccharide-inflamed Rat Dental Pulp Reviewed

    Naoto Ohkura, Yoshimi Shigetani, Nagako Yoshiba, Kunihiko Yoshiba, Takashi Okiji

    JOURNAL OF ENDODONTICS   40 ( 8 )   1112 - 1117   2014.8

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    DOI： 10.1016/j.joen.2013.12.024

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  • M2 Macrophages Participate in the Biological Tissue Healing Reaction to Mineral Trioxide Aggregate Reviewed

    Takafumi Ito, Tomoatsu Kaneko, Yusuke Yamanaka, Yoshimi Shigetani, Kunihiko Yoshiba, Takashi Okiji

    JOURNAL OF ENDODONTICS   40 ( 3 )   379 - 383   2014.3

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    DOI： 10.1016/j.joen.2013.11.011

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  • Localization of SUMOylation factors and Osterix in odontoblast lineage cells during dentin formation and regeneration Reviewed

    Akihiro Hosoya, Akira Yukita, Tadashi Ninomiya, Toru Hiraga, Kunihiko Yoshiba, Nagako Yoshiba, Etsuo Kasahara, Hiroaki Nakamura

    HISTOCHEMISTRY AND CELL BIOLOGY   140 ( 2 )   201 - 211   2013.8

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    DOI： 10.1007/s00418-013-1076-y

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  • Odontoblast response to cavity preparation with Er:YAG laser in rat molars: an immunohistochemical study Reviewed

    Yoshimi Shigetani, Hironobu Suzuki, Hayato Ohshima, Kunihiko Yoshiba, Nagako Yoshiba, Takashi Okiji

    ODONTOLOGY   101 ( 2 )   186 - 192   2013.7

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  • ヒト歯髄創傷治癒過程における細胞外基質の局在変化 Fibrillin-1基質の動的リモデリングに関する検索 Reviewed

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 重谷 佳見, 武井 絵梨花, 細矢 明宏, 中村 浩彰, 興地 隆史

    日本歯科保存学雑誌   56 ( 3 )   161 - 168   2013.6

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  • Mineral trioxide aggregateに対するラット皮下結合組織の応答 マクロファージ関連分子の免疫組織化学的・分子生物学的解析 Reviewed

    伊藤 崇史, 山中 裕介, 金子 友厚, 吉羽 邦彦, 吉羽 永子, 重谷 佳見, 興地 隆史

    日本歯科保存学雑誌   56 ( 1 )   9 - 16   2013.2

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  • Evaluation of the responses of MHC class II molecule-expressing cells and macrophages to epoxy resin-based and 4-META-containing, methacrylate resinbased root canal sealers in rat subcutaneous tissue Reviewed

    Yusuke Yamanaka, Yoshimi Shigetani, Kunihiko Yoshiba, Tomoatsu Kaneko, Nagako Yoshiba, Takashi Okiji

    Dental Materials Journal   32 ( 5 )   822 - 827   2013

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  • Two Distinct Processes of Bone-like Tissue Formation by Dental Pulp Cells after Tooth Transplantation Reviewed

    Akihiro Hosoya, Akira Yukita, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Hiroaki Nakamura

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   60 ( 11 )   861 - 873   2012.11

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  • Immunohistochemical analysis of two stem cell markers of alpha-smooth muscle actin and STRO-1 during wound healing of human dental pulp Reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Yoshimi Shigetani, Erika Takei, Akihiro Hosoya, Hiroaki Nakamura, Takashi Okiji

    HISTOCHEMISTRY AND CELL BIOLOGY   138 ( 4 )   583 - 592   2012.10

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  • Thy-1-positive cells in the subodontoblastic layer possess high potential to differentiate into hard tissue-forming cells Reviewed

    Akihiro Hosoya, Toru Hiraga, Tadashi Ninomiya, Akira Yukita, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Susumu Ito, Hiroaki Nakamura

    HISTOCHEMISTRY AND CELL BIOLOGY   137 ( 6 )   733 - 742   2012.6

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  • Gene Expression Analysis of Membrane Transport Proteins in Normal and Lipopolysaccharide-inflamed Rat Dental Pulp Reviewed

    Naoto Ohkura, Yoshimi Shigetani, Nagako Yoshiba, Kunihiko Yoshiba, Takashi Okiji

    JOURNAL OF ENDODONTICS   38 ( 5 )   648 - 652   2012.5

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  • Expression of Angiogenic Factors in Rat Periapical Lesions Reviewed

    Yusuke Yamanaka, Tomoatsu Kaneko, Kunihiko Yoshiba, Reika Kaneko, Nagako Yoshiba, Yoshimi Shigetani, Jacques E. Noer, Takashi Okiji

    JOURNAL OF ENDODONTICS   38 ( 3 )   313 - 317   2012.3

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  • Expressional Alterations of Fibrillin-1 during Wound Healing of Human Dental Pulp Reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Naoto Ohkura, Akihiro Hosoya, Yoshimi Shigetani, Yusuke Yamanaka, Naoya Izumi, Hiroaki Nakamura, Takashi Okiji

    JOURNAL OF ENDODONTICS   38 ( 2 )   177 - 184   2012.2

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  • Mineral trioxide aggregates : Physicochemical and biological properties and their clinical implications

    Takashi OKIJI, Linlin HAN, Yoshimi SHIGETANI, Kunihiko YOSHIBA

    The Journal of Japan Endodontic Association   33 ( 1 )   3 - 13   2012

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    DOI： 10.20817/jeajournal.33.1_3

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  • Immunohistochemical analysis of subcutaneous tissue reactions to methacrylate resin-based root canal sealers Reviewed

    Y. Yamanaka, Y. Shigetani, K. Yoshiba, N. Yoshiba, T. Okiji

    INTERNATIONAL ENDODONTIC JOURNAL   44 ( 7 )   669 - 675   2011.7

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    DOI： 10.1111/j.1365-2591.2011.01874.x

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  • 半導体レーザー照射後のラット臼歯における非コラーゲンタンパクの遺伝子発現 Reviewed

    重谷 佳見, 大倉 直人, 吉羽 邦彦, 吉羽 永子, 大島 勇人, 興地 隆史

    日本歯科保存学雑誌   53 ( 5 )   495 - 501   2010.10

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  • Potential of periodontal ligament cells to regenerate alveolar bone Reviewed

    Akihiro Hosoya, Tadashi Ninomiya, Toru Hiraga, Kunihiko Yoshiba, Nagako Yoshiba, Etsuo Kasahara, Hidehiro Ozawa, Hiroaki Nakamura

    Journal of Oral Biosciences   52 ( 2 )   72 - 80   2010

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  • Immunohistochemical analysis of nestin, osteopontin, and proliferating cells in the reparative process of exposed dental pulp capped with mineral trioxide aggregate Reviewed

    Momoko Kuratate, Kunibiko Yosbiba, Yosbimi Sbigetani, Nagako Yosbiba, Hayato Obsbima, Takashi Okiji

    JOURNAL OF ENDODONTICS   34 ( 8 )   970 - 974   2008.8

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    DOI： 10.1016/j.joen.2008.03.021

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  • Alveolar bone regeneration of subcutaneously transplanted rat molar Reviewed

    Akihiro Hosoya, Tadashi Ninomiya, Toru Hiraga, Chen Zhao, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Takahiro Okabe, Shigeyuki Wakitani, Hirohito Yamada, Etsuo Kasahara, Hidehiro Ozawa, Hiroaki Nakamura

    BONE   42 ( 2 )   350 - 357   2008.2

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    DOI： 10.1016/j.bone.2007.09.054

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  • Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse mandible development Reviewed

    Nagako Yoshiba, Kunihiko Yoshiba, Akihiro Hosoya, Masahiro Saito, Takamasa Yokoi, Takashi Okiji, Norio Amizuka, Hidehiro Ozawa

    CELL AND TISSUE RESEARCH   330 ( 1 )   133 - 145   2007.10

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s00441-007-0439-x

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  • Immunohistochemical study of hard tissue formation in the rat pulp cavity after tooth replantation Reviewed

    Chen Zhao, Akihiro Hosoya, Hiroshi Kurita, Tao Hu, Toru Hiraga, Tadashi Ninomiya, Kunihiko Yoshiba, Nagako Yoshiba, Masafumi Takahashi, Kenji Kurashina, Hidehiro Ozawa, Hiroaki Nakamura

    ARCHIVES OF ORAL BIOLOGY   52 ( 10 )   945 - 953   2007.10

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    DOI： 10.1016/j.archoralbio.2007.04.015

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  • Hard tissue formation in subcutaneously transplanted rat dental pulp Reviewed

    A. Hosoya, H. Nakamura, T. Ninomiya, K. Hoshi, K. Yoshiba, N. Yoshiba, M. Takahashi, T. Okabe, N. Sahara, H. Yamada, E. Kasahara, H. Ozawa

    JOURNAL OF DENTAL RESEARCH   86 ( 5 )   469 - 474   2007.5

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    DOI： 10.1177/154405910708600515

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  • Immunohistochemical localization of alpha-smooth muscle actin during rat molar tooth development Reviewed

    Akihiro Hosoya, Hiroaki Nakamura, Tadashi Ninomiya, Kunihiko Yoshiba, Nagako Yoshiba, Hiroyuki Nakaya, Shigeyuki Wakitani, Hirohito Yamada, Etsuo Kasahara, Hidehiro Ozawa

    JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY   54 ( 12 )   1371 - 1378   2006.12

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    DOI： 10.1369/jhc.6A6980.2006

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  • Differential regulation of TIMP-1,-2, and-3 mRNA and protein expressions during mouse incisor development Reviewed

    N Yoshiba, K Yoshiba, C Stoetzel, F Perrin-Schmitt, Y Cam, JV Ruch, A Hosoya, H Ozawa, H Lesot

    CELL AND TISSUE RESEARCH   324 ( 1 )   97 - 104   2006.4

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    DOI： 10.1007/s00441-005-0123-y

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  • Odontoblast responses to GaAlAs laser irradiation in rat molars: an experimental study using heat-shock protein-25 immunohistochemistry Reviewed

    Y Tate, K Yoshiba, N Yoshiba, M Iwaku, T Okiji, H Ohshima

    EUROPEAN JOURNAL OF ORAL SCIENCES   114 ( 1 )   50 - 57   2006.2

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    DOI： 10.1111/j.1600-0722.2006.00261.x

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  • Immunohistochemical Study of Osteodentin in the Unerupted Rat Incisor Reviewed

    Akihiro Hosoya, Hiroaki Nakamura, Shoji Akahane, Kunihiko Yoshiba, Nagako Yoshiba, Tadashi Ninomiya, Kazuto Hoshi, Noriyuki Sahara, Etsuo Kasahara, Hidehiro Ozawa

    journal of oral biosciences   48 ( 2 )   132 - 137   2005

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    DOI： 10.2330/joralbiosci.48.132

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  • Temporospatial gene expression and protein localization of matrix metalloproteinases and their inhibitors during mouse molar tooth development Reviewed

    N Yoshiba, K Yoshiba, C Stoetzel, F Perrin-Schmitt, Y Cam, JV Ruch, H Lesot

    DEVELOPMENTAL DYNAMICS   228 ( 1 )   105 - 112   2003.9

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    DOI： 10.1002/dvdy.10352

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  • Class II antigen-presenting dendritic cell and nerve fiber responses to cavities, caries, or caries treatment in human teeth Reviewed

    K Yoshiba, N Yoshiba, M Iwaku

    JOURNAL OF DENTAL RESEARCH   82 ( 6 )   422 - 427   2003.6

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    DOI： 10.1177/154405910308200604

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  • An immunohistochemical study on hard tissue formation in a subcutaneously transplanted rat molar Reviewed

    A Hosoya, K Yoshiba, N Yoshiba, KT Hoshi, M Iwaku, H Ozawa

    HISTOCHEMISTRY AND CELL BIOLOGY   119 ( 1 )   27 - 35   2003.1

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    DOI： 10.1007/s00418-002-0478-z

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  • Clinical and Statistical Evaluation of Cleft Palate Team Activities at Niigata University Dental Hospital

    ASAHITO Toshikazu, TERADA Kazuto, ONO Kazuhiro, YAGI Minoru, KOBAYASHI Tadaharu, IIDA Akihiko, NOMURA Akiko, SATO Takahiro, YOSHIBA Nagako, TAI Hideaki, ISHII Kazuhiro, TAGUCHI Yo, KOBAYASHI Fukiko, SEO Kenji, TERAO Emiko, TAKAGI Ritsuo, HANADA Kooji

    日本口蓋裂学会雑誌   27 ( 3 )   297 - 305   2002.10

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  • Odontoblast processes in human dentin revealed by fluorescence labeling and transmission electron microscopy Reviewed

    K Yoshiba, N Yoshiba, S Ejiri, M Iwaku, H Ozawa

    HISTOCHEMISTRY AND CELL BIOLOGY   118 ( 3 )   205 - 212   2002.9

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    DOI： 10.1007/s00418-002-0442-y

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  • Immunohistochemical study on pulpal response in rat molars after cavity preparation by Er : YAG laser Reviewed

    K Tanabe, K Yoshiba, N Yoshiba, M Iwaku, H Ozawa

    EUROPEAN JOURNAL OF ORAL SCIENCES   110 ( 3 )   237 - 245   2002.6

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  • Distribution of noncollagenous proteins during reparative dentinogenesis in human teeth Reviewed

    K Yoshiba, N Yoshiba, M Iwaku, H Ozawa

    DENTIN/PULP COMPLEX   157 - 158   2002

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  • Hard tissue formation in subcutaneously transplanted rat molars Reviewed

    A Hosoya, K Yoshiba, N Yoshiba, M Iwaku, K Hoshi, H Ozawa

    DENTIN/PULP COMPLEX   166 - 167   2002

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  • Differential expression of laminin-5 subunits during incisor and molar development in the mouse Reviewed

    K Yoshiba, N Yoshiba, D Aberdam, G Meneguzzi, F Perrin-Schmitt, C Stoetzel, JV Ruch, H Lesot

    INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY   44 ( 3 )   337 - 340   2000.4

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  • Immunohistochemical localization of laminin-5 and integrin A6 beta 4 during cytodifferentiation of ameloblasts in the mouse incisor Reviewed

    K Yoshiba, N Yoshiba, M Iwaku, H Ozawa

    JOURNAL OF INVESTIGATIVE DERMATOLOGY   113 ( 6 )   1143 - 1143   1999.12

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  • Immunohistochemical localizations of class II antigens and nerve fibers in human carious teeth: HLA-DR immunoreactivity in Schwann cells Reviewed

    N Yoshiba, K Yoshiba, M Iwaku, H Ozawa

    ARCHIVES OF HISTOLOGY AND CYTOLOGY   61 ( 4 )   343 - 352   1998.10

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    DOI： 10.1679/aohc.61.343

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  • Expression and localization of laminin-5 subunits in the mouse incisor Reviewed

    N Yoshiba, K Yoshiba, D Aberdam, G Meneguzzi, F Perrin-Schmitt, C Stoetzel, JV Ruch, H Lesot

    CELL AND TISSUE RESEARCH   292 ( 1 )   143 - 149   1998.4

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    DOI： 10.1007/s004410051044

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  • Expression and localization of laminin-5 subunits during mouse tooth development Reviewed

    K Yoshiba, N Yoshiba, D Aberdam, G Meneguzzi, F Perrin-Schmitt, C Stoetzel, JV Ruch, H Lesot

    DEVELOPMENTAL DYNAMICS   211 ( 2 )   164 - 176   1998.2

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    DOI： 10.1002/(SICI)1097-0177(199802)211:2<164::AID-AJA5>3.0.CO;2-F

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  • Immunohistochemical localization of HLA-DR-positive cells in unerupted and erupted normal and carious human teeth Reviewed

    N Yoshiba, K Yoshiba, H Nakamura, M Iwaku, H Ozawa

    JOURNAL OF DENTAL RESEARCH   75 ( 8 )   1585 - 1589   1996.8

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    DOI： 10.1177/00220345960750081001

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  • Immunolocalization of fibronectin during reparative dentinogenesis in human teeth after pulp capping with calcium hydroxide Reviewed

    K Yoshiba, N Yoshiba, H Nakamura, M Iwaku, H Ozawa

    JOURNAL OF DENTAL RESEARCH   75 ( 8 )   1590 - 1597   1996.8

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    DOI： 10.1177/00220345960750081101

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  • Immunolocalization of the small proteoglycan decorin in human teeth Reviewed

    N Yoshiba, K Yoshiba, M Iwaku, H Ozawa

    ARCHIVES OF ORAL BIOLOGY   41 ( 4 )   351 - 357   1996.4

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  • Distribution of the small proteoglycan decorin in human teeth Reviewed

    N Yoshiba, K Yoshiba, M Iwaku, H Ozawa

    DENTIN/PULP COMPLEX   304 - 305   1996

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  • IMMUNOELECTRONMICROSCOPIC STUDY OF THE LOCALIZATION OF FIBRONECTIN IN THE ODONTOBLAST LAYER OF HUMAN TEETH Reviewed

    N YOSHIBA, K YOSHIBA, H NAKAMURA, M IWAKU, H OZAWA

    ARCHIVES OF ORAL BIOLOGY   40 ( 2 )   83 - 89   1995.2

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  • EFFECTS OF ANTIBACTERIAL CAPPING AGENTS ON DENTAL PULPS OF MONKEYS MECHANICALLY EXPOSED TO ORAL MICROFLORA Reviewed

    K YOSHIBA, N YOSHIBA, M IWAKU

    JOURNAL OF ENDODONTICS   21 ( 1 )   16 - 20   1995.1

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    DOI： 10.1016/S0099-2399(06)80551-0

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  • HISTOLOGICAL OBSERVATIONS OF HARD-TISSUE BARRIER FORMATION IN AMPUTATED DENTAL-PULP CAPPED WITH ALPHA-TRICALCIUM PHOSPHATE-CONTAINING CALCIUM HYDROXIDE Reviewed

    K YOSHIBA, N YOSHIBA, M IWAKU

    ENDODONTICS & DENTAL TRAUMATOLOGY   10 ( 3 )   113 - 120   1994.6

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  • A CONFOCAL LASER-SCANNING MICROSCOPIC STUDY OF THE IMMUNOFLUORESCENT LOCALIZATION OF FIBRONECTIN IN THE ODONTOBLAST LAYER OF HUMAN TEETH Reviewed

    N YOSHIBA, K YOSHIBA, M IWAKU, H NAKAMURA, H OZAWA

    ARCHIVES OF ORAL BIOLOGY   39 ( 5 )   395 - 400   1994.5

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  • Histological observations of hard tissue barrier formation in amputated dental pulp capped with α‐tricalcium phosphate containing calcium hydroxide Reviewed

    K. Yoshiba, N. Yoshiba, M. Iwaku

    Dental Traumatology   10 ( 3 )   113 - 120   1994

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    DOI： 10.1111/j.1600-9657.1994.tb00535.x

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Books

  • Distribution of noncollagenous proteins during reparative dentinogenesis in human teeth.

    Dentin/Pulp Comples:Proceeding of the International Conference on Dentin/Pulp Complex 2001.  2002 

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  • Distribution of concollagenous proteins during reparative dentinogensis in human teeth.

    Dentin/Pulp Comples:Proceeding of the International Conference on Dentin/Pulp Complex 2001.  2002 

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  • Distribution of odontoblast processes in human coronal dentin. (共著)

    Dentin/Pulp Complex : Proceedings of the International Confernce on Dentin/Pulp Complex 1995. Quintessence Publishing Co.  1996 

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  • Distribution of the small proteoglycan decorin in human teeth. (共著)

    Dentin/Pulp Complex : Proceedings of the International Conference on Dentin/Pulp Complex 1995. Quintessence Publishing Co.  1996 

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  • Hard tissue formation in subcutaneously transplanted rat molars.

    Dentin/Pulp Complex:Proceeding of the International Conference on Dentin/Pulp Complex 2001. Quintessence Publishing Co. 

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  • Hard tissue formation in subcutaneously transplanted rat molars.

    Dentin/Pulp Comples:Proceeding of the International Conference on Dentin/Pulp Complex 2001.Quintessence Publishing Co. 

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MISC

  • Dystrophic Calcification and Accumulation of Non-Collagenous Proteins on the Pulp Wound Site after Pulpotomy

    枝並直樹, 高原信太郎, 大倉直人, 吉羽邦彦, 吉羽永子, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   160th   2024

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  • 再生歯内療法モデルラットにおける歯根の成長段階に応じた治癒の変化と間葉系幹細胞の挙動との関係性

    高原信太郎, 大倉直人, 吉羽永子, BALDEON-GUTIERREZ Rosa, GOMEZ-KASIMOTO Susan, 枝並直樹, 井田貴子, 竹中彰治, 野杁由一郎

    新潟歯学会雑誌   54 ( 2 )   2024

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  • The localization of various mesenchymal stem cell marker-positive cells in early healing stage after regenerative endodontic procedure

    高原信太郎, 大倉直人, 吉羽永子, 竹中彰治, 枝並直樹, 吉羽邦彦, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   159th   2023

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  • Impact of the tissue nonspecific alkaline phosphatase during the root formation

    大倉直人, 大倉直人, 吉羽永子, 高原信太郎, GUTIERREZ Rosa Edith Baldeon, GOMEZ-KASIMOTO Susan, 井田貴子, 枝並直樹, 竹中彰治, 吉羽邦彦, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   159th   2023

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  • The comparison analyses of wound-healing mechanism according to the root development stage using the regeneration model rats

    高原信太郎, 大倉直人, 吉羽邦彦, 吉羽永子, 竹中彰治, 枝並直樹, 庭野和明, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   158th   2023

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  • Interactions between Apically-extruded Bioceramic Sealers and periodontal tissues

    高原信太郎, 枝並直樹, 竹中彰治, 吉羽邦彦, 大倉直人, 吉羽永子, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   157th   2022

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  • Comparison of Biomineralization Ability of Calcium Silicate-based and Calcium Hydroxide-based Intracanal Medicaments

    枝並直樹, 竹中彰治, 吉羽邦彦, 大倉直人, 吉羽永子, 高原信太郎, 野杁由一郎

    日本歯科保存学会学術大会プログラムおよび講演抄録集(Web)   157th   2022

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  • ヒト歯髄においてシュワン細胞はマクロファージをM2型へ転換する

    吉羽永子, 大倉直人, 前川知樹, 泉健次, 細矢明宏, 中村浩彰, 前田健康, 野杁由一郎, 吉羽邦彦

    Journal of Oral Biosciences Supplement (Web)   2019   2019

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  • 歯髄創傷モデルラットを用いた修復象牙質形成時におけるGlut1-Runx2関連の解析

    竹内 亮祐, 大倉 直人, 枝並 直樹, 遠間 愛子, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 2 )   113 - 114   2018.12

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  • 歯髄創傷治癒モデルラットを用いたグルコース輸送担体Glut2とGlut4の局在および遺伝子発現の解析

    遠間 愛子, 大倉 直人, 枝並 直樹, 竹内 亮祐, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 2 )   114 - 114   2018.12

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  • マイクロスコープを用いた再歯根尖切除術の1例

    大倉 直人, 山本 信一, 阿部 達也, 竹内 亮祐, 遠間 愛子, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 1 )   29 - 35   2018.6

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  • マイクロスコープを用いた再歯根尖切除術の1例

    大倉 直人, 山本 信一, 阿部 達也, 竹内 亮祐, 遠間 愛子, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    新潟歯学会雑誌   48 ( 1 )   29 - 35   2018.6

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  • 歯髄創傷治癒モデルラットを用いたGlucose Transporter-4の局在および遺伝子発現の解析

    遠間 愛子, 大倉 直人, 枝並 直樹, 竹内 亮祐, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   147回   46 - 46   2017.10

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  • 歯髄創傷治癒過程におけるマクロファージの集積とmyofibroblast様細胞の分化

    枝並 直樹, 吉羽 邦彦, 吉羽 永子, 大倉 直人, 竹内 亮祐, 遠間 愛子, 野杁 由一郎

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   147回   182 - 182   2017.10

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  • 歯髄創傷治癒モデルラットを用いたGlucose Transporter-1およびrunt-related transcription factor 2の局在と遺伝子発現解析

    竹内 亮祐, 大倉 直人, 枝並 直樹, 遠間 愛子, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   147回   86 - 86   2017.10

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  • ヒト歯髄組織創傷治癒過程における骨髄由来間葉系前駆細胞fibrocyteの動態検索

    吉羽 永子, 大倉 直人, 細矢 明宏, 中村 浩彰, 野杁 由一郎, 吉羽 邦彦, 枝並 直樹, 遠間 愛子, 竹内 亮介

    Journal of Oral Biosciences Supplement   2017   427 - 427   2017.9

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  • ラット臼歯断髄後におけるmyofibroblastの動態解析

    枝並 直樹, 吉羽 永子, 大倉 直人, 野杁 由一郎, 吉羽 邦彦

    新潟歯学会雑誌   47 ( 1 )   52 - 52   2017.6

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  • ヒト歯髄組織創傷治癒過程における骨髄由来間葉系前駆細胞fibrocyteの動態検索

    吉羽永子, 大倉直人, 細矢明宏, 中村浩彰, 野杁由一郎, 吉羽邦彦

    Journal of Oral Biosciences Supplement (Web)   2017   2017

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  • 各種ケイ酸カルシウム系セメントの生体機能性と直接覆髄後の歯髄反応

    吉羽 邦彦, 枝並 直樹, 日向 剛, 韓 臨麟, 竹内 亮祐, 遠間 愛子, 大倉 直人, 武井 絵梨花, 吉羽 永子, 興地 隆史

    日本歯科医師会雑誌   69 ( 5 )   454 - 454   2016.8

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  • 培養ヒト歯髄に対するprostaglandin EP4レセプターアゴニストの影響

    大倉 直人, 吉羽 永子, 吉羽 邦彦, 小田 陽平, 興地 隆史

    日本歯科医師会雑誌   69 ( 5 )   454 - 454   2016.8

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  • 培養ヒト歯髄に対するprostaglandin EP2レセプターアゴニストの影響

    大倉 直人, 枝並 直樹, 竹内 亮祐, 遠間 愛子, 吉羽 永子, 吉羽 邦彦, 小田 陽平, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   144回   124 - 124   2016.6

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  • ラット臼歯におけるMTAによる直接覆髄後のGlucose Transporter-2の免疫組織化学および遺伝子発現の解析

    遠間 愛子, 大倉 直人, 枝並 直樹, 竹内 亮祐, 吉羽 永子, 吉羽 邦彦

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   144回   111 - 111   2016.6

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  • マイクロスコープを用いた再歯根尖切除術の1症例

    大倉 直人, 山本 信一, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 野杁 由一郎

    日本歯内療法学会学術大会プログラム・抄録集   37回   60 - 60   2016.6

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  • ラット臼歯におけるMineral trioxide aggregateによる直接覆髄後のGlucose Transporter-1の免疫局在および遺伝子発現解析

    竹内 亮祐, 大倉 直人, 枝並 直樹, 遠間 愛子, 吉羽 永子, 吉羽 邦彦

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   144回   112 - 112   2016.6

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  • ラット皮下組織における4-META含有レジン系シーラーの生体親和性 Reviewed

    枝並 直樹, 重谷 佳見, 吉羽 邦彦, 日向 剛, 吉羽 永子, 興地 隆史

    日本歯科保存学雑誌   59 ( 1 )   65 - 73   2016.2

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  • 実験的歯の移動におけるラット臼歯歯髄内prostaglandin I2合成酵素と受容体の発現解析

    大倉 麻里子, 大倉 直人, 吉羽 永子, 吉羽 邦彦, 依田 浩子, 大島 勇人, 齋藤 功, 興地 隆史

    新潟歯学会雑誌   45 ( 2 )   97 - 98   2015.12

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  • ケイ酸カルシウム系覆髄材の生体機能性 ラット皮下組織内埋入によるin vivoの検討

    日向 剛, 吉羽 邦彦, 韓 臨麟, 枝並 直樹, 吉羽 永子, 興地 隆史

    新潟歯学会雑誌   45 ( 2 )   109 - 109   2015.12

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  • 培養ヒト歯髄に対するprostaglandin EP4レセプターアゴニストの影響

    大倉 直人, 吉羽 永子, 吉羽 邦彦, 小田 陽平, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   143回   75 - 75   2015.11

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  • 各種ケイ酸カルシウム系セメントによるラット臼歯直接覆髄後の被蓋硬組織形成

    枝並 直樹, 吉羽 邦彦, 武井 絵梨花, 日向 剛, 竹内 亮祐, 遠間 愛子, 重谷 佳見, 吉羽 永子, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   143回   148 - 148   2015.11

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  • ラット臼歯歯髄断髄後のProstaglandin Transporterに対する免疫組織学的局在解析

    大倉 直人, 枝並 直樹, 吉羽 永子, 吉羽 邦彦, 依田 浩子, 大島 勇人, 興地 隆史

    Journal of Oral Biosciences Supplement   2015   367 - 367   2015.9

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  • 培養ヒト歯髄の各種遺伝子発現に対するprostaglandin EP4レセプターアゴニストの影響

    大倉 直人, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    日本歯内療法学会学術大会プログラム・抄録集   36回   71 - 71   2015.7

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  • ラット臼歯歯髄断髄後のProstaglandin Transporterに対する免疫組織学的局在解析

    大倉直人, 枝並直樹, 吉羽永子, 吉羽邦彦, 依田浩子, 大島勇人, 興地隆史

    Journal of Oral Biosciences Supplement (Web)   2015   2015

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  • ヒト歯髄におけるプロスタグランジンE2輸送担体および特異的レセプターの免疫組織化学的局在解析

    大倉 直人, 大倉 麻里子, 吉羽 永子, 吉羽 邦彦, 小田 陽平, 依田 浩子, 大島 勇人, 興地 隆史

    Journal of Oral Biosciences Supplement   2014   183 - 183   2014.9

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  • ヒト歯髄におけるProstaglandinレセプターの免疫組織学的局在解析

    大倉 直人, 重谷 佳見, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    日本歯内療法学会学術大会プログラム・抄録集   35回   101 - 101   2014.7

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  • ラット臼歯におけるMineral Trioxide Aggregateによる直接覆髄後のM2マクロファージの動態

    武井 絵梨花, 重谷 佳見, 吉羽 邦彦, 日向 剛, 吉羽 永子, 興地 隆史

    新潟歯学会雑誌   44 ( 1 )   55 - 56   2014.6

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  • ヒト歯髄におけるプロスタグランジンE<sub>2</sub>輸送担体および特異的レセプターの免疫組織化学的局在解析

    大倉直人, 大倉麻里子, 吉羽永子, 吉羽邦彦, 小田陽平, 依田浩子, 大島勇人, 興地隆史

    Journal of Oral Biosciences Supplement (Web)   2014   2014

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  • ラット炎症歯髄に対する薬物輸送担体を介したProstaglandin E2輸送経路解析

    大倉 直人, 重谷 佳見, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    新潟歯学会雑誌   43 ( 2 )   155 - 155   2013.12

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  • ラット臼歯矯正移動時における歯髄内prostanoid receptorの遺伝子発現と免疫組織学的局在解析

    大倉 直人, 大倉 麻里子, 重谷 佳見, 吉羽 永子, 吉羽 邦彦, 齋藤 功, 興地 隆史

    Journal of Oral Biosciences Supplement   2013   189 - 189   2013.9

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  • ヒト歯髄組織からoutgrowthする細胞による組織構築に関する研究

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 細矢 明宏, 中村 浩彰, 興地 隆史

    Journal of Oral Biosciences Supplement   2013   193 - 193   2013.9

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  • ラット臼歯矯正移動時における歯髄内prostanoid receptorの遺伝子発現と免疫組織学的局在解析

    大倉直人, 大倉麻里子, 重谷佳見, 吉羽永子, 吉羽邦彦, 齋藤功, 興地隆史

    Journal of Oral Biosciences Supplement (Web)   2013   ROMBUNNO.P2‐24 (WEB ONLY)   2013

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  • ヒト歯髄組織からoutgrowthする細胞による組織構築に関する研究

    吉羽永子, 吉羽邦彦, 大倉直人, 細矢明宏, 中村浩彰, 興地隆史

    Journal of Oral Biosciences Supplement (Web)   2013   2013

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  • ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    Journal of Oral Biosciences Supplement   2012   160 - 160   2012.9

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  • ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    日本歯科医師会雑誌   65 ( 5 )   628 - 628   2012.8

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  • 半導体レーザー照射後のラット臼歯における硬組織形成誘導機構の解明

    重谷 佳見, 大倉 直人, 細矢 明宏, 鈴木 啓展, 吉羽 邦彦, 吉羽 永子, 大島 勇人, 興地 隆史

    日本歯科医師会雑誌   65 ( 5 )   629 - 629   2012.8

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  • ラット実験的根尖歯周炎の成立過程における血管新生関連遺伝子の発現

    山中 裕介, 金子 友厚, 吉羽 邦彦, 伊藤 崇史, 吉羽 永子, 重谷 佳見, 興地 隆史

    新潟歯学会雑誌   42 ( 1 )   62 - 62   2012.6

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  • ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉直人, 重谷佳見, 細矢明宏, 吉羽永子, 吉羽邦彦, 興地隆史

    Journal of Oral Biosciences Supplement (Web)   2012   2012

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  • ラット実験的炎症歯髄におけるプロスタノイド受容体遺伝子発現の経時的解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   134回   104 - 104   2011.5

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  • ラット炎症歯髄に対する薬物輸送担体の遺伝子発現解析

    大倉 直人, 重谷 佳見, 細矢 明宏, 吉羽 永子, 吉羽 邦彦, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   133回   96 - 96   2010.10

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  • ヒト歯髄創傷治癒過程で生じるFibrillin-1の分解は細胞分化と石灰化を誘導する

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 細矢 明宏, 重谷 佳見, 興地 隆史

    特定非営利活動法人日本歯科保存学会学術大会プログラムおよび講演抄録集   132回   117 - 117   2010.5

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  • 半導体レーザー照射後のラット臼歯における硬組織関連タンパクの遺伝子発現

    重谷 佳見, 大倉 直人, 吉羽 邦彦, 吉羽 永子, 興地 隆史

    日本歯内療法学会学術大会プログラム・抄録集   31回   110 - 110   2010.5

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  • 半導体レーザー照射後のラット臼歯における硬組織関連タンパクの遺伝子発現

    重谷佳見, 大倉直人, 吉羽邦彦, 吉羽永子, 興地隆史

    日本歯内療法学会学術大会プログラム・抄録集   31st   2010

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  • Mineral trioxide aggregate(MTA)の物理化学的特性と直接覆髄後の歯髄反応

    吉羽 邦彦, 鞍立 桃子, 重谷 佳見, 韓 臨麟, 吉羽 永子, 興地 隆史

    新潟歯学会雑誌   39 ( 2 )   181 - 182   2009.12

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  • 半導体レーザー照射に対するラット臼歯歯髄初期反応

    笹 なつき, 重谷 佳見, 吉羽 邦彦, 吉羽 永子, 監物 新一, 大島 勇人, 興地 隆史

    Journal of Oral Biosciences   51 ( Suppl. )   100 - 100   2009.8

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  • 早期臨床実習への窩洞形成修復実習の導入

    HAN Linlin, 興地隆史, 吉羽永子, 小林哲夫, 藤井規孝, 小野和宏, 前田健康

    日本歯科医学教育学会総会・学術大会プログラム・抄録集   28th   128   2009

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  • Bone-like tissue formation in the pulp cavity after tooth replantation

    HOSOYA Akihiro, CHEN Zhao, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro, NAKAMURA Hiroaki

    51   88 - 88   2008.5

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  • 歯根膜組織の歯槽骨再生能

    細矢 明宏, 平賀 徹, 中村 浩彰, 吉羽 邦彦, 吉羽 永子, Zhao Chen, 高橋 将文, 岡部 高弘, 脇谷 滋之, 山田 博仁, 笠原 悦夫, 二宮 禎, 小澤 英浩

    THE BONE   22 ( 1 )   3 - 7   2008.1

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  • MTAによるラット臼歯覆髄モデルにおける歯髄反応の免疫組織化学的解析

    鞍立 桃子, 吉羽 邦彦, 重谷 佳見, 吉羽 永子, 大島 勇人, 興地 隆史

    新潟歯学会雑誌   37 ( 2 )   249 - 250   2007.12

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  • Association of TIMP-2 with extracellular matrix exposed to mechanical stress and its co-distribution with periostin during mouse tooth development Reviewed

    N. Yoshiba, K. Yoshiba, A. Hosoya, M. Saito, T. Yokoi, T. Okiji, N. Amizuka, H. Ozawa

    European Cells and Materials   14 ( SUPPL.2 )   142   2007.11

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  • MTAによるラット臼歯覆髄モデルにおける歯髄反応

    鞍立 桃子, 吉羽 邦彦, 重谷 佳見, 吉羽 永子, 大島 勇人, 興地 隆史

    Journal of Oral Biosciences   49 ( Suppl. )   114 - 114   2007.8

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  • ラット歯髄皮下移植後の硬組織形成

    細矢 明宏, 中村 浩彰, 星 和人, 吉羽 邦彦, 吉羽 永子, 高橋 将文, 岡部 高弘, 山田 博仁, 笠原 悦男, 二宮 禎, 佐原 紀行, 小澤 英浩

    THE BONE   21 ( 4 )   399 - 403   2007.7

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  • 歯の形態形成と細胞分化におけるTIMP-1,-2,-3のmRNAとタンパクの発現

    吉羽 永子, 吉羽 邦彦, 興地 隆史

    新潟歯学会雑誌   37 ( 1 )   47 - 48   2007.7

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  • An immunohistochemical study on pulpal responses to mineral trioxide aggregate in human teeth

    YOSHIBA Kunihiko, YOSHIBA Nagako, SHIGETANI Yoshimi, HOSOYA Akihiro, OKIJI Takashi

    50   138 - 138   2007.5

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  • 歯周組織発生過程におけるα-平滑筋アクチンの局在と歯槽骨形成との関連

    細矢 明宏, 中村 浩彰, 吉羽 邦彦, 吉羽 永子, 中谷 宏幸, 脇谷 滋之, 山田 博仁, 笠原 悦男, 二宮 禎, 小澤 英浩

    THE BONE   21 ( 3 )   281 - 285   2007.5

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  • 歯髄の潜在的硬組織形成能

    細矢明宏, 中村浩彰, 二宮 禎, 星 和人, 吉羽邦彦, 吉羽永子, 高橋将文, 岡部高弘, 佐原紀行, 山田博仁, 笠原悦男, 小澤英浩

    The BONE   21(4)   399 - 403   2007

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  • An immunohistochemical study on pulpal responses to mineral trioxide aggregate in rat molars

    KURATATE Momoko, YOSHIBA Kunihiko, SHIGETANI Yoshimi, YOSHIBA Nagako, OKIJI Takashi

    49   150 - 150   2006.10

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  • Alveolar bone regeneration after tooth transplantation into subcutaneous tissue

    HOSOYA Akihiro, NAKAMURA Hiroaki, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    49   42 - 42   2006.10

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  • マウス歯の発生過程におけるTIMP-2とPeriostinは類似の時間的空間的発現パターンを示す

    吉羽 永子, 吉羽 邦彦, 興地 隆史, 斎藤 正寛, 横井 隆政, 細矢 明宏, 網塚 憲生, 小澤 英浩

    Journal of Oral Biosciences   48 ( Suppl. )   153 - 153   2006.9

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  • Expression of TIMP-2 and Periostin during Mouse Tooth Development

    YOSHIBA Nagako, YOSHIBA Kunihiko, OKIJI Takashi, SAITO Masahiro, YOKOI Takamasa, HOSOYA Akihiro, OZAWA Hidehiro

    49   98 - 98   2006.4

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  • Immunohistochemical Localization of α-SMA during rat molar tooth development

    HOSOYA Akihiro, NAKAMURA Hiroaki, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    48   59 - 59   2005.10

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  • 歯科用レーザーのう蝕治療への応用に関する研究 レーザー照射に対する歯髄反応について

    吉羽 邦彦, 楯 泰昌, 吉羽 永子, 岩久 正明, 興地 隆史, 大島 勇人

    歯界展望   特別号 ( 健康な心と身体は口腔から-発ヨコハマ2004- )   274 - 274   2005.6

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  • ラット臼歯への半導体レーザー照射に対する歯髄反応

    楯 泰昌, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 興地 隆史, 大島 勇人

    新潟歯学会雑誌   34 ( 2 )   288 - 288   2005.1

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  • Gene Expression and Protein Localization of MMP-2, -9, MT1-MMP and TIMP-1, -2, -3 During Mouse Molar Tooth Development

    YOSHIBA Nagako, YOSHIBA Kunihiko, OKIJI Takashi, HOSOYA Akihiro, OZAWA Hidehiro

    47   195 - 195   2004.10

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  • Immunohistochemical Study of Hard Tissue Formation in a Subcutaneously-transplanted Rat Dental Pulp

    HOSOYA Akihiro, YOSHIBA Kunihiko, YOSHIBA Nagako, YAMADA Hirohito, KASAHARA Etsuo, OZAWA Hidehiro

    47   27 - 27   2004.10

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  • マウス切歯発生過程におけるTIMPsの発現

    吉羽 永子, 吉羽 邦彦, 興地 隆史, 細矢 明宏, 小澤 英浩

    Journal of oral biosciences   46 ( 5 )   451 - 451   2004.9

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  • 歯髄の硬組織形成機構に関する微細構造学的研究 ラット切歯歯髄皮下移植実験モデルを用いた検討

    細矢 明宏, 中村 浩彰, 星 和人, 佐原 紀行, 二宮 禎, 吉羽 邦彦, 吉羽 永子, 小澤 英浩

    Journal of Oral Biosciences   46 ( 5 )   377 - 377   2004.9

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  • 歯科用レーザーのう蝕治療への応用に関する研究 レーザー照射に対する歯髄反応について

    吉羽 邦彦, 楯 泰昌, 吉羽 永子, 岩久 正明, 興地 隆史, 大島 勇人

    日本歯科医師会雑誌   57 ( 4 )   401 - 401   2004.7

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  • Immunohistochemical study on pulpal response of rat molars to irradiation by semiconductor laser

    TATE Yasuaki, YOSHIBA Kunihiko, YOSHIBA Nagako, SHIGETANI Yoshimi, OKIJI Takashi, IWAKU Masaaki

    46   117 - 117   2003.10

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  • マウス臼歯発生過程におけるMMPsおよびTIMPsの発現

    吉羽 邦彦, 吉羽 永子, 小澤 英浩

    歯科基礎医学会雑誌   45 ( 5 )   293 - 293   2003.9

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  • ラット皮下移植歯髄の硬組織誘導能に関する免疫組織化学的研究

    細矢 明宏, 星 和人, 吉羽 邦彦, 吉羽 永子, 笠原 悦男, 小澤 英浩

    歯科基礎医学会雑誌   45 ( 5 )   295 - 295   2003.9

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  • ラット臼歯における半導体レーザー照射に対する歯髄反応

    楯 泰昌, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 大島 勇人

    歯科基礎医学会雑誌   45 ( 5 )   295 - 295   2003.9

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  • An immunohistochemical study of hard tissue formation in the pulp cavity of rat molar after transplantation into subcutaneous tissue. Reviewed

    A. Hosoya, K. Yoshiba, N. Yoshiba, K. Hoshi, M. Iwaku, H. Ozawa

    JOURNAL OF DENTAL RESEARCH   82   B252 - B252   2003.6

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  • Responses of MHC class II molecule-expressing cells to cavity preparation and caries treatment.

    K. Yoshiba, N. Yoshiba, M. Iwaku

    JOURNAL OF DENTAL RESEARCH   82   B187 - B187   2003.6

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  • Immunohistochemical Distribution of Antigen Presenting Cells After Cavity Preparation and Caries Treatment

    YOSHIBA Kunihiko, YOSHIBA Nagako, IWAKU Masaaki

    46   102 - 102   2003.5

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  • ラット臼歯の皮下移植後に観察される歯髄腔内硬組織形成

    細矢 明宏, 小澤 英浩, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 星 和人

    THE BONE   17 ( 2 )   3 - 6   2003.3

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  • ラット臼歯の皮下移植後に形成される歯髄腔内硬組織形成

    細矢明宏, 吉羽邦彦, 吉羽永子, 星和人, 岩久正明, 小澤英浩

    The BONE   17(2)   107 - 110   2003

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  • ラット切歯先端部硬組織の免疫組織化学的研究

    細矢 明宏, 星 和人, 吉羽 邦彦, 吉羽 永子, 笠原 悦男, 小澤 英浩

    歯科基礎医学会雑誌   44 ( 5 )   417 - 417   2002.9

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  • う蝕治療へのEr:YAG laserの応用

    重谷 佳見, 田辺 啓太, 楯 泰昌, 吉羽 邦彦, 吉羽 永子, 岡本 明, 子田 晃一, 岩久 正明

    新潟歯学会雑誌   32 ( 1 )   83 - 84   2002.7

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    Other Link： http://search.jamas.or.jp/link/ui/2003032120

  • 臨床予備実習における客観的臨床能力試験(OSCE)の試み

    子田 晃一, 岡本 明, 福島 正義, 吉羽 邦彦, 吉羽 永子, 韓 臨麟, 庭野 和明, 石崎 裕子, 竹中 彰治, 富田 文仁

    日本歯科保存学雑誌   45 ( 春季特別 )   167 - 167   2002.4

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  • Expression of non-collagenous proteins and TGF-bs during reparative dentinogenesis.

    K Yoshiba, N Yoshiba, M Iwaku

    JOURNAL OF DENTAL RESEARCH   81   A155 - A155   2002.3

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  • マウス切歯歯胚における半接着斑関連タンパクの局在

    吉羽 邦彦, 吉羽 永子, 岩久 正明, 小澤 英浩

    歯科基礎医学会雑誌   43 ( 5 )   566 - 566   2001.8

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  • ラット臼歯皮下移植実験モデルにおける歯髄腔内硬組織形成に関する免疫組織化学的研究

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    歯科基礎医学会雑誌   43 ( 5 )   569 - 569   2001.8

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  • 歯髄の石灰化に関する免疫組織化学的研究 ラット臼歯皮下移植実験モデルを用いた検討

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    日本歯科保存学雑誌   44 ( 春季特別 )   21 - 21   2001.4

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  • ラット臼歯の皮下移植後に形成される歯髄腔内硬組織に関する免疫組織化学的研究

    細矢 明宏, 吉羽 邦彦, 吉羽 永子, 星 和人, 岩久 正明, 小澤 英浩

    新潟歯学会雑誌   30 ( 2 )   268 - 268   2000.12

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  • マウス歯胚発生過程におけるラミニンー5の特異的発現

    吉羽 邦彦, 吉羽 永子, 岩久 正明

    歯科基礎医学会雑誌   42 ( 5 )   460 - 460   2000.8

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  • Er YAGレーザーを用いたラット臼歯窩洞形成後の歯髄反応に関する免疫組織化学的研究

    田辺 啓太, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 小澤 英浩

    歯科基礎医学会雑誌   42 ( 5 )   456 - 456   2000.8

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  • Er:YAGレーザーによる窩洞形成後の歯髄反応に関する免疫組織化学的研究 ラット臼歯を用いた基礎的研究

    田辺 啓太, 吉羽 邦彦, 吉羽 永子, 岩久 正明, 小澤 英浩

    新潟歯学会雑誌   29 ( 2 )   208 - 209   1999.12

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  • Immunohistochemical study on pulpal response in rat molars after cavity preparation by Er:YAG Laser

    TANABE Keita, YOSHIBA Kunihiko, YOSHIBA Nagako, IWAKU Masaaki, OZAWA Hidehiro

    42   66 - 66   1999.10

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  • エナメル芽細胞分化過程におけるラミニン-5とα6β4インテグリンの局在

    吉羽 邦彦, 吉羽 永子, 岩久 正明, 小澤 英浩

    歯科基礎医学会雑誌   41 ( 5 )   442 - 442   1999.8

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  • Expression and localization of Laminin-5 and Integrins in Mouse Tooth.

    YOSHIBA Kunihiko, YOSHIBA Nagako, IWAKU Masaaki, OZAWA Hidehiro

    41   167 - 167   1998.10

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  • Immunohistochemical Localizations of Class II Antigens and Nerve Fibers in Human Carious Teeth.

    YOSHIBA Nagako, YOSHIBA Kunihiko, IWAKU Masaaki, OZAWA Hidehiro

    41   165 - 165   1998.10

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  • Distribution of Odontoblast Processes in Human Dentin

    YOSHIBA Kunihiko, YOSHIBA Nagako, EJIRI Sadakazu, IWAKU Masaaki, OZAWA Hidehiro

    日本歯科保存学雑誌   40   117 - 117   1997.5

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  • Immunolocalization of the Small Proteoglycan Decorin in Human Teeth

    YOSHIBA Nagako, YOSHIBA Kunihiko, IWAKU Masaaki, OZAWA Hidehiro

    40   118 - 118   1997.5

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  • DISTRIBUTION OF FIBRONECTIN DURING DENTIN BRIDGE FORMATION AFTER PULP CAPPING Reviewed

    K YOSHIBA, N YOSHIBA, M IWAKU, H NAKAMURA, H OZAWA

    JOURNAL OF DENTAL RESEARCH   73   318 - 318   1994

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  • DISTRIBUTION OF FIBRONECTIN IN ODONTOBLAST LAYER OF HUMAN TEETH

    N YOSHIBA, K YOSHIBA, M IWAKU, H NAKAMURA, H OZAWA

    JOURNAL OF DENTAL RESEARCH   73   121 - 121   1994

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  • ORAL HEALTH OF A WORKING-AGED POPULATION IN AN AGING AREA

    M FUKUSHIMA, K YOSHIBA, N YOSHIBA, M IWAKU

    JOURNAL OF DENTAL RESEARCH   73   235 - 235   1994

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  • Epidemiological Survey of Oral Disease in an Adult Population : Prevalence of Periodontal Disease and Root Surface Caries.

    Japanese Journal of Conservative Dentistry   36 ( 1 )   295 - 302   1993

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  • Evaluation of Various Twbed Media for Efficient Bacteriological Examination in Endodontics

    Takaaki Kiryu, Naomi Kurihara, Toshiyuki Hinata

    Niigata Dental Journal   22 ( 1 )   15 - 20   1992

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    Other Link： http://search.jamas.or.jp/link/ui/1994145453

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Presentations

  • Differences in affinity between laminin isoforms and their integrins affect macrophage phenotype Invited

    Nagako Yoshiba

    The 97th Annual Meeting of the Japanese Biochemical Society  2024.11 

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    Event date： 2024.11

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  • Integrin α7 regulates the differentiation of THP-1 macrophages into dendritic cells

    Yoshiba N., Maekawa T., Sekiguchi K., Kaku M., Sato Y., Rosenkranz A., Maeda T., Yoshiba K.

    The 56th Annual Meeting of the Japanese Society for Matrix Biology and Medicine  2024.6 

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    Event date： 2024.6

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Awards

  • 令和3年度新潟大学優秀論文賞

    2021.12   新潟大学  

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  • 学術賞

    2014   日本歯科保存学会  

    吉羽 永子

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  • 奨励賞

    1998   日本歯科保存学会  

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    Country：Japan

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  • 海外派遣助成賞

    1995   財団法人山下太郎  

    吉羽 永子

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Research Projects

  • 海洋生物由来接着剤とペプチド修飾を併用したインプラント周囲軟組織の新規付着技術

    Grant number：25K13047

    2025.4 - 2028.3

    System name：科学研究費助成事業

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    齋藤 夕子, 山田 雄二, 吉羽 永子, 泉 健次

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • The analyses of the internalization mechanism and delivery pathway of P gingivalis-OMV at he oral-brain interface

    Grant number：25K13017

    2025.4 - 2028.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • マクロファージの表現型に影響する細胞外基質ラミニンの機能解析

    Grant number：23K24517

    2024.4 - 2026.3

    System name：科学研究費助成事業

    Research category：基盤研究(B)

    Awarding organization：日本学術振興会

    吉羽 永子, 前田 健康, 前川 知樹, 大倉 直人

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    Grant amount：\7800000 （ Direct Cost: \6000000 、 Indirect Cost：\1800000 ）

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  • Functional analysis of extracellular matrix laminin affecting macrophage phenotype

    Grant number：22H03259

    2022.4 - 2026.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\17160000 （ Direct Cost: \13200000 、 Indirect Cost：\3960000 ）

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  • 歯髄の創傷治癒・再生過程におけるGli1陽性幹細胞の動態と分化誘導機構の解明

    Grant number：21K09914

    2021.4 - 2024.3

    System name：科学研究費助成事業 基盤研究(C)

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    吉羽 邦彦, 吉羽 永子, 枝並 直樹, 細矢 明宏, 入江 一元

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    Grant amount：\4160000 （ Direct Cost: \3200000 、 Indirect Cost：\960000 ）

    歯の保存には歯髄の保護・保存が重要であり、直接覆髄や一部生活歯髄切断など歯髄保存療法が、また失われた歯髄に対しては再生歯内療法が試みられている。しかし根管内に形成される硬組織はセメント質あるいは骨様組織であり、理想的な「象牙質・歯髄複合体の再生」には至っていない。また、より迅速かつ確実な処置法の開発が望まれている。本研究では、歯髄の創傷治癒・再生過程において中心的役割を果たすと考えられている間葉系幹細胞の動態について、転写因子Gli1発現をマーカーとして細胞系譜解析により検索するとともに、覆髄材・根管充填材として注目されているバイオセラミックス配合材料の歯髄創傷治癒に与える影響について検討した。
    遺伝子改変(Gli1-CreERT2/Tomato)マウスにおいて、Gli1陽性細胞は歯根膜および歯髄の血管周囲に散在性に認められること、また、臼歯歯根膜から分取されたGli1陽性細胞はコロニー形成能、多分化能を示し幹細胞特性を持つことが明らかにされた。これらの結果から、再生歯内療法応用後の治癒過程、特に硬組織形成におけるGli1陽性細胞の関与が示唆された。一方、バイオセラミックス配合覆髄材・根管充填材のin vitro・in vivoにおけるアパタイト析出能を検討した結果、すべての被験材料は疑似体液中でその表面にCa-Pを含むアパタイト様構造物を析出させたが、ラット皮下移植実験では、材料間にその析出能の差異が認められた。また、レジン含有ケイ酸カルシウム（MTA）系セメントは断髄後、CD68陽性マクロファージの持続的な浸潤と修復象牙質形成の遅延が観察され、材料選択の重要性が示唆された。

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  • シュワン細胞がマクロファージを神経保護作用を有する表現型に誘導する機序の解明

    2021.4 - 2022.3

    System name：科学技術人材育成費補助金「ダイバーシティ研究環境実現イニシアティブ（先端型）」

    Awarding organization：文部科学省

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  • ヒト歯髄の創傷治癒過程におけるM2マクロファージとシュワン細胞の相互作用の解明

    Grant number：19K10146

    2019.4 - 2022.3

    System name：科学研究費助成事業 基盤研究(C)

    Research category：基盤研究(C)

    Awarding organization：日本学術振興会

    吉羽 永子, 吉羽 邦彦, 大倉 直人, 枝並 直樹

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    免疫機能の中心的役割を担っているマクロファージは、その誘導因子により、異なる性質を持つ２つの分化型に分化することが知られている。すなわちM1マクロファージと称される炎症を促進するものと、その反対にM2マクロファージという炎症を抑制し組織の修復に働くタイプのものである。本研究では、ヒト歯髄組織におけるマクロファージの特にM2型の動態について、in vivoおよびin vitroにおいて解析している。
    令和元年度では先ずin vivoすなわち、(1)ヒトの健全歯髄組織、(2)覆髄剤であるMTAを用いた直接覆髄後の創傷治癒過程、さらに(3)様々な病態のう蝕歯髄におけるM2マクロファージの動態を検索した。その結果、これら全ての状態において、CD163をマーカーとするM２マクロファーは神経線維保護機能を有するシュワン細胞と共在していることが明らかとなった。シュワン細胞はp75 nerve growth factor receptor (NGFR)を発現していることから、そのリガンドの１つであるbrain-derived neurotrophic factor (BDNF)の局在を調べたところ、それらCD163陽性のM2マクロファージはBDNFを発現していることが確認された。シュワン細胞とM2マクロファージの相互作用をさらに解析するために、ヒト歯髄組織からシュワン細胞を取り出し、in vitroにおいてTHP-1細胞由来マクロファージ(M0)との共培養を試みた。その結果、シュワン細胞に接触しとどまっているTHP-1マクロファージは、その形を球状から紡錘形に変化させ、CD163陽性のM2マクロファージに分化することが明らかとなった。歯髄は神経線維が非常に豊富な組織である。シュワン細胞はその神経線維を物理的にあるいは様々なサイトカインを分泌することで直接的に保護している。一方で、シュワン細胞は、神経線維を破壊するM1型マクロファージをM2型に変化させることで神経線維を保護していることが示唆された。

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  • The clarification of the pulp generation mechanism to improve the odontoblast differentiation by the transporter of ascorbic acid.

    Grant number：19K10147

    2019.4 - 2020.3

    System name：Grants-in-Aid for Scientific Research

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

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  • A study on the mechanisms of induction and differentiation of stem cells during wound healing and regeneration of dentin-pulp complex

    Grant number：16H05516

    2016.4 - 2020.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko

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    Grant amount：\17030000 （ Direct Cost: \13100000 、 Indirect Cost：\3930000 ）

    This study aimed to elucidate the mechanism of dental pulp wound healing and reparative dentinogenesis. We investigated the cellular events and expression of related factors after direct pulp capping or pulpotomy. The results suggested that α-SMA-positive myofibroblasts are progenitors of odontoblast-like cells and that TGF-β1 and EDA-fibronectin are involved in their differentiation. In addition, bone marrow-derived mesenchymal cells, fibrocytes, appeared transiently in the early stages and M2 phenotype macrophages colocalized with Schwann cells in healthy as well as inflamed pulp. It was suggested that various types of cells are involved in pulp wound healing and repair process.

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  • Role of alpha-SMA expressing cells in dental pulp wound healing and regeneration

    Grant number：16K11546

    2016.4 - 2019.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    Yoshiba Nagako

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    Dental pulp is a soft connective tissue encased in mineralized dentine. When dentine continuity is disrupted by caries or traumatic injury, the resident odontoblasts are also destroyed at that site. Pulp capping agents can help to cover the site through the production of a mineralized matrix through the activation of newly differentiated odontoblast-like cells, however, the exact mechanisms of the process have not been fully revealed. The present study has demonstrated that α-SMA expressing cells play a crucial role in the wound healing.

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  • Regeneration of rat molar pulp tissue by the implantation of stem cells from incisor pulp: development of a rat model of autologous pulp tissue engineering

    Grant number：26293405

    2014.4 - 2017.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi

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    Grant amount：\16250000 （ Direct Cost: \12500000 、 Indirect Cost：\3750000 ）

    This study aimed to establish an experimental autologous coronal pulp regeneration model using rat molars and examine whether co-implantation of endothelial cells with stem cells accelerates pulp tissue regeneration. Rat bone marrow mesenchymal stem cells (MSCs) with PLLA/peptide hydrogel constructs were implanted into the coronal pulp chamber of pulpotomized maxillary first molars of Wistar rats. One week after the implantation, a pulp-like tissue was generated in the pulp chamber. In teeth in which rat endothelial cells were co-implanted with MSCs, gene expression levels of pro-angiogenic factors such as Cxcl1 and dentin sialophosphoprotein were elevated compared with MSC-implanted teeth. The co-implanted teeth also showed accelerated scaffold absorption and complete dentin bridge formation. A similar analysis is in progress using stem cells isolated from rat incisor pulp tissues.

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  • Contribution of Myofibroblasts in Dental Pulp Healing and Regeneration

    Grant number：25462952

    2013.4 - 2016.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA NAGAKO, YOSHIBA KUNIHIKO, OHKURA NAOTO

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    Grant amount：\4810000 （ Direct Cost: \3700000 、 Indirect Cost：\1110000 ）

    Alpha-smooth muscle actin (α-SMA) is a marker of myofibroblasts, which play a central role in wound healing. Fibrillin-1 is a major constituent of microfibrils and an extracellular-regulator of TGF-β1, an important cytokine for myofibroblasts differentiation. We examined alterations of α-SMA and fibrillin-1 expression in organotypic culture of dental pulp. After 7 days of culture, most fibroblasts and odontoblasts were immunoreactive for α-SMA with a significant increase of α-SMA mRNA expression. Furthermore, immunostaining of fibrillin-1 became faint with mRNA downregulation. Administration of inhibitors for extracellular matrix proteases resulted in the recovery of fibrillin-1 immunostaining, and fibroblasts lost their immunoreactivity for α-SMA with mRNA downregulation. These findings suggest that fibrillin-1 degradation and downregulation might be implicated in the myofibroblasts differentiation in dental pulp wound healing.

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  • Application of activated macrophages derived from dental pulp stem cells to dental pulp tissue engineering

    Grant number：25670808

    2013.4 - 2015.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category：Grant-in-Aid for Challenging Exploratory Research

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi, YOSHIBA Nagako, YOSHIBA Kunihiko, KANEKO Tomoatsu, SHIGETANI Yoshimi, OHKURA Naoto

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    This study aimed to examine the role of macrophages in the regeneration of dental pulp tissues. After co-implantation of ED2-positive macrophages isolated from rat dental pulp with stem cells into the coronal pulp chamber of pulpotomized rat molars, expression of macrophage markers in the engineered pulp tissue was analyzed. When IL-4 treated ED2-positive macrophages were co-implanted with stem cells, the engineered tissues showed a significant increase in the number of ED2-positive cells and the expression of CD34 and CD163 mRNAs. These findings suggest that M2 macrophages show proliferation and act as wound healing macrophages after co-implantation of macrophages with stem cells.

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  • A study on the mechanisms of tissue wound healing and regeneration of dental pulp

    Grant number：24592863

    2012.4 - 2015.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA KUNIHIKO, YOSHIBA Nagako

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    Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）

    The aim of this study was to elucidate cellular events during pulp tissue wound healing and reparative dentin formation after direct pulp capping. M2 macrophage-associated molecule-expressing cells transiently accumulated beneath the exposure site. The deposition of osteopontin and dentin matrix protein 1 (DMP1) at exposed pulp sites preceded the appearance of nestin-immunoreactive cells, active cell proliferation and new matrix formation. These suggest that M2 macrophages participate in the initial phases of the healing and that osteopontin and DMP1 act as a trigger of pulp repair. In addition, numerous α-smooth muscle actin (SMA)-positive cells emerged at the wound margin, and the initially formed mineralized barrier was lined with α-SMA-positive cells similar in appearance to reparative odontoblasts, some of which co-expressed nestin. Fibrillin-1 degradation and down-regulation might be implicated in the differentiation of α-SMA-positive cells in this process.

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  • Dental pulp regeneration by stem cell transplantation: development of scaffolds and establishment of an animal experimental model

    Grant number：23390433

    2011.4 - 2014.3

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi, YOSHIBA Nagako, YOSHIBA Kunihiko, OHSHIMA Hayato, KANEKO Tomoatsu, SHIGETANI Yoshimi

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    Grant amount：\18720000 （ Direct Cost: \14400000 、 Indirect Cost：\4320000 ）

    This study was designed with the ultimate purpose of establishing a tooth pulp tissue engineering using transplantation of dental pulp stem cells, and conducted to select appropriate scaffolds and develop an experimental engineering system using rat molars. It was demonstrated that rat dental pulp is equipped with stem-like cells that coexpress CD146 and MAP1B and are distributed predominantly in theperivascular area. rat dental pulp by means of immunohistochemistry. Moreover, transplantation of rat mesenchymal stem cells into pulpotomized rat molars with a PLLA/Puramatrix scaffold resulted in the formation of new mineralized tissues at 4 weeks. These results suggest that the experimental model used in this study is useful for investigating the pulp tissue regeneratiopn using stem cell transplantation.

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  • Elucidation of the mechanism of post-repantation replacement resorption as a basis for the development of periodontal ligament regeneration therapy

    Grant number：23659887

    2011 - 2012

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

    Research category：Grant-in-Aid for Challenging Exploratory Research

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi, YOSHIBA Kunihiko, YOSHIBA Nagako, SHIGETANI Yoshimi, KANEKO Tomoatsu, YAMANAKA Yusuke, ITO Takafumi, HINATA Go

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    Grant amount：\3640000 （ Direct Cost: \2800000 、 Indirect Cost：\840000 ）

    External replacement resorption, characterized by the fusion of the bone and tooth root (ankylosis), is known as an uncontrollable complication after tooth replantation. This study was conducted as an initial exploration of the pathogenic mechanisms of post-replantation replacement resorption. Experimental replantation of rat molars were carried out in two different conditions (immediate replantation and replantation after sodium hypochlorite immersion), and pathological changes of the pulpal and periodontalligament (PDL) tissues were examined at 1 to 3 weeks postooperatively by means of histology and immunohistochemistry. Results demonstrated that (i) ankylotic changes in the PDL, (ii) bone-like tissue formation in the pulp, and (iii) CD68-expressing macrophage infiltration in the pulp and PDL were more prominent in the NaClO-immersed group than in the immediately replanted group. These findings suggest that severe damage to the PDL cells remaining on the root surface triggers the development of the above-mentioned pathological changes.

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  • Degradation and down-regulation of fibrillin-1 during wound healing of human dental pulp tissue

    Grant number：22592119

    2010 - 2012

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Nagako, YOSHIBA Kunihiko

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

    Degradation of fibrillins, the major constituents of microfibrils, is known to facilitate therelease of active transforming growth factor-β (TGF-β), a signaling molecule contributing tomineralized tissue barrier formation in exposed dental pulps. To examine the involvement offibrillins in the barrier formation, temporospatial expression of (i) genes and proteins offibrillins, and (ii) factors possibly associated with fibrillin degradation and cytodifferentiationwere examined in exposed human pulps. Human pulp slice cultures were also examined for therole of fibrillins in mineralization. Degradation and downregulation of fibrillin-1 expressiontook place during the mineralized tissue barrier formation in exposed pulps in vivo as well as in pulp slice cultures, which should be correlated with the temporary appearance ofα-SMA-positive fibroblasts and pulpal tissue mineralization.

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  • A study on the mechanisms of tissue repair and regeneration of dentin-pulp complex

    Grant number：21592417

    2009 - 2011

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko, YOSHIBA Nagako, SHIGETANI Yoshimi

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

    The aim of this study was to elucidate cellular events during pulp tissue repair and reparative dentin formation after tooth injury. The up-regulation ofα-smooth muscle actin(SMA) was characteristically observed in fibroblastic cells in an organ culture system of rat molar. Thy-1-positive dental pulp cells localized in the subodontoblastic layer had the ability to differentiate into hard tissue-forming cells. Theα-SMA-positive and/or Thy-1-positive cells may play a role in tissue repair and regeneration of dental pulp.

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  • Pathogenic mechanisms in apical periodontitis : innate immunity, acquired immunity and dendritic cell maturation

    Grant number：20390483

    2008 - 2010

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi, YOSHIBA Kunihiko, YOSHIBA Nagako, OHSHIMA Hayato, SHIGETANI Yoshimi, KANEKO Tomoatsu

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    Grant amount：\16770000 （ Direct Cost: \12900000 、 Indirect Cost：\3870000 ）

    This study aimed to advance the understanding of the involvement of dendritic cells and immunoregulatory molecules in the pathogenic mechanisms in apical periodontitis. Results demonstrated that unsealed pulp exposure caused the upregulation of MHC class II molecules, CD86, CD83, TLR2 and TLR4 mRNAs in the periodontal ligament of rat molars, as revealed by laser microdissection and real time PCR. Moreover, by employing a whole tooth culture system of the rat molar, it was demonstrated that resident macrophages and dendritic cells upregulated the expression of CD14, TLR4 and CX3CR1 following LPS stimulation.

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  • A study of pulpal responses to laser irradiation

    Grant number：19592197

    2007 - 2009

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Nagako, YOSHIBA Kunihiko, TAKENAKA Shohji

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    Grant amount：\4550000 （ Direct Cost: \3500000 、 Indirect Cost：\1050000 ）

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  • 歯内歯周疾患の病態形成機序-新規疾患モデルを用いた樹状細胞の動態解析

    Grant number：19659496

    2007 - 2008

    System name：科学研究費助成事業 萌芽研究

    Research category：萌芽研究

    Awarding organization：日本学術振興会

    興地 隆史, 吉羽 邦彦, 吉羽 永子

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    Grant amount：\3200000 （ Direct Cost: \3200000 ）

    樹状細胞は生体内で最も有力な抗原提示細胞であり、この機能を通じて外来抗原刺激に対する免疫応答の発動と質の決定という重要な役割を演じる。これらの細胞が根分岐部における生体防御機構の発動様式の特異性に密接に関連すると推定されるが、根分岐部病変に対する適切な動物モデルは現在まで開発されておらず、根分岐部歯根膜で営まれる免疫防御機構の実態は不明のままである。本研究ではこの点に着目し、新たな実験的根分岐部病変誘発法を採用し、樹状細胞を中心とする各種免疫担当細胞の動態の検索を通じて根分岐部病変の成立・持続過程で営まれる免疫機構の解明をはかることを目的とするものである。
    本年度は先ず、ラット臼歯歯根膜の種々の部位(根分岐部,根尖部,近心側,遠心側)における抗原提示細胞の成熟度,活性化度の相違を検索することを目的として,major histocompatibility complex(MHC)クラスII分子,CD86,CD83およびToll-like receptor(TLR)4のmRNA発現をリアルタイムPCR法を用いて定量解析した.その結果,全ての検索対象遺伝子とも、最も口腔環境に近接した部位である根分岐部において発現レベルが著明に高く,根尖部においては低レベルであった.従って、ラット正常歯根膜の各部位には,細菌刺激の多寡などの微小環境の相違に応じて、成熟度,活性化度の異なる抗原提示細胞が存在することが示唆された.さらに、ラット臼歯を1日間露髄開放し,正常時と露髄開放後の分岐部歯根膜における上記mRNA発現をリアルタイムPCR法を用いて定量,比較したところ,各遺伝子とも開放1日経過後で有意に増加した.従って、ラット臼歯の根分岐部歯根膜に存在する抗原提示細胞が,歯髄の感染に起因する細菌刺激侵襲に応じて,速やかに成熟度や活性化度を増加させることが示唆された.

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  • A study on mechanisms of tissue repair and regeneration of the dentin-pulp complex

    Grant number：18592085

    2006 - 2008

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko, YOSHIBA Nagako, HOSOYA Akihiro

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    Grant amount：\4020000 （ Direct Cost: \3600000 、 Indirect Cost：\420000 ）

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  • Immune defense mechanisms of the dentin/pulp complex: Immunohistochemical analysis on the heterogeneity and kinetics of dendritic cells

    Grant number：17390508

    2005 - 2007

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

    Research category：Grant-in-Aid for Scientific Research (B)

    Awarding organization：Japan Society for the Promotion of Science

    OKIJI Takashi, YOSHIBA Kunihiko, YOSHIBA Nagako, OHSHIMA Hayato

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    Grant amount：\14340000 （ Direct Cost: \13500000 、 Indirect Cost：\840000 ）

    This study investigated dendritic cell (DC) subpopulations and co-stimulatory molecule-expressing cells in pulpitis and apical periodontitis by means of immunohistochemistry and transmission electron microscopy.
    (1) Pulpitis and apical periodontitis were induced in rat molars by making unsealed pulp exposures, and kinetics of DCs was investigated by means of immunoelectron microscopy for MHC class II molecules, CD11c, CD86 and OX62 (a marker for rat DC subpopulation). Results demonstrated that DCs in normal periodontal ligament and periapical lesions consisted of two subpopulations: the subpopulations differently expressed CD11c and OX62 and might differ in lineage, state of maturation and function. In the induced periapical lesions, CD86-expressing cells, comprising approximately 10% of MHC class II molecule-expressing cells, were frequently distributed in the vicinity of nerve fibers, suggesting the involvement of mature DC-nerve interaction in the development of periapical lesions. Moreover, kinetics of DCs during wound healing process of exposed rat molar pulps was investigated after 1VITA-capping, which constantly induced pulp healing with dentin bridge formation. It was demonstrated that DC-like cells showed an accumulation subjacent to the wound surface during initial healing process of the exposed pulps.
    (2) Immunohistochemistry and electron microscopy for human apical periodontitis revealed that DCs expressing BLA-DR were mainly distributed in lymphocyte-rich areas. By means of laser microdisection and RT-PCR analysis, it was demonstrated that upregulation of CD83 and CD86 on DCs and CD28 on T lymphocytes occurred in the lymphocyte-rich areas. These findings may indicate that DCs act as antigen presenting cells that stimulate T lymphocyte activation.

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  • Evaluation of pulpal responses to GaAIAs laser irradiation.

    Grant number：16591909

    2004 - 2006

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Nagako, YOSHIBA Kunihiko, TAKENAKA Shoji

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    Grant amount：\3500000 （ Direct Cost: \3500000 ）

    This study aimed to evaluate the effect of the GaAIAs laser on dentin-pulp complex, in order to establish the potential applications of the laser for clinical practice in caries treatment.
    1. Immunohistochemical analysis of caries teeth.
    Major histocompatibility complex (MHC) class II molecule-expressing cells are distributed in human dental pulp, and have been show to accumulate beneath caries lesions. After caries treatment, clusters consisting of class II molecule-expressing dendritic cells, T-lymphocytes, and nerve fibers still remained locally in the subodontoblastic area. Under active and deep caries, a number of STRO-1-positive stem cells have been recognized along blood vessels.
    2. Responses of GaAIAs laser irradiation to dentin-pulp complex in rat molars.
    The medial surface of the molar was lased at an output power of 0.5-1.5 W for 180s. At 7days after irradiation, tertiary dentin has been formed. At 30 days, tertiary dentin with/without bone-like tissue was formed abundantly in the dental pulp. Statistical analysis revealed that the area occupied by the new hard tissues was significantly wider in 1.5W-lased speciments than in 0.5W-lased speciments.
    3. Responses of GaAIAs laser irradiation to dentin-pulp complex in human teeth.
    The volunteers, who had been scheduled to undergo extraction for various therapeutic reasons, were enrolled in the study. Informed consent was obtained from subjects after the proposed study was fully explained. Class V circular preparations were cut into the buccal surfaces, and the cavity was irradiated by GaAIAs laser, and then filled with composite resin. As a control, the cavity was filled without the laser irradiation. Under deep cavities, class II molecule-expressing dendritic cells displaced the injured odontoblasts in control, while few dendritic cells displaced the injured odontoblasts in the lased teeth.

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  • A study on mechanisms of tissue formation and regeneration of the dentin-pulp complex

    Grant number：16591910

    2004 - 2005

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko, YOSHIBA Nagako, HOSOYA Akihiro, OZAWA Hidehiro

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    Grant amount：\3600000 （ Direct Cost: \3600000 ）

    This study aims to elucidate mechanisms of tissue formation and regeneration of the dentin-pulp complex. The results were as follows :
    1. During mouse tooth development, the expression of an intermediate filament nestin was intense in differentiating odontoblasts, and became restricted to the secretory pole of functional odontoblasts, suggesting that nestin plays a role in terminal differentiation, especially in cell elongation and/or polarization of odontoblasts.
    2. Distinct temporal and spatial expression patterns of TIMPs suggest divergent functions of these factors in incisor organogenesis. Intense expression of Timp-1 was detected in differentiating odontoblasts, while Timp-3 was expressed by subodontoblasts, suggesting their involvement in odontoblast differentiation.
    3. The unerupted rat incisor was composed of osteodentin, with numerous cells present in the anterior apex. The osteodentin was immunopositive for osteocalcin, bone sialoprotein, and dentin sialoprotein, with an immunolocalization pattern similar to that of dentin. These results indicate that osteodentin in the rat incisor possesses a dentin-like characteristics.
    4. We performed a histological and immunohistochemical evaluation of mineralized tissue induced by pulp transplantation into subcutaneous tissue. The results indicate that pulp cells are able to form hard tissue with bone- or cementum-like characteristics without dentin influence. Calcification may start in necrotic cells and matrix vesicles, followed by collagenous calcification.
    5. Pulpal responses to GaAlAs laser irradiation were elucidated. The results indicated that the GaAlAs laser may induce the formation of tertiary dentin by influencing the secretory activity of odontoblasts. However, higher energies may cause irreversible changes to the pulp, often leading to the formation of an intrapulpal bone-like tissue.

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  • A study on mechanisms of tissue repair and regeneration of the dentin-pulp complex

    Grant number：14571811

    2002 - 2003

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko, YOSHIBA Nagako, IWAKU Masaaki

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    Grant amount：\3900000 （ Direct Cost: \3900000 ）

    This study aims to elucidate mechanisms of tissue repair and/or regeneration of the dentin-pulp complex. Several factors involved in cell differentiation during tooth development and reparative dentinogenesis were analyzed.
    The results were as follows :
    1.During mouse molar tooth development, MMP-2,-9,and MT1-MMP were expressed in the dental epithelium and mesenchyme. In contrast, TIMPs(1-3) were differentially expressed. The distinct temporospatial distribution patterns of the TIMPs suggest that these inhibitors play several intrinsic roles during tooth development.
    2.The odontoblast-like cells forming reparative dentin expressed TGF-βs, especially β2 and β3, and also TGF-β type II receptor, suggesting that cells that form reparative dentin express odontoblast phenotype and that TGF-βs may be involved in the differentiation of replacement odontoblasts during reparative dentinogenesis after pulp capping.
    3.Cavity preparation in normal teeth caused alteration in the distribution of MHC class II molecule-expressing cells, although this change appears to be reversible. By contrast, in the caries-removed and restored teeth, antigen presentation and cellular and/or humoral immunoresponses would seem to persist, even after treatment.
    4.The pulpal responses to the irradiation of tooth surfaces with an 810nm-GaAlAs semiconductor laser were evaluated in the rat molars. This laser at certain power settings could induce the formation of tertiary dentin without hard tissue injury nor evoking inflammatory reactions in the pulp.

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  • う蝕修復処置後の歯髄反応に関する免疫組織化学的研究

    Grant number：13771127

    2001 - 2002

    System name：科学研究費助成事業 若手研究(B)

    Research category：若手研究(B)

    Awarding organization：日本学術振興会

    吉羽 永子

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    Grant amount：\2100000 （ Direct Cost: \2100000 ）

    本研究は、より生物学的な歯髄保護材開発のための基礎的研究の環として、免疫担当細胞、特に抗原提示細胞、炎症性細胞ならびに神経線維の分布、局在が歯髄疾患の病態を把握する指標となり得るかどうかを検討するとともに、う蝕修復処置後の歯髄治癒過程におけるこれらの動態を免疫組織化学的、微細構造学的に検索するものである。研究要旨の同意を得られた抜去適応の健全あるいはう蝕歯を用い、従来の臨床術式に則し、う蝕検知液下にてう蝕を可久的に除去し、また細菌感染のある歯髄組織の修復過程と比較するために健全歯を用い、様々な深さの窩洞を形成し、レジン充填処置を施し、一定期間経過後抜去して試料を得て検討し、以下の結果が得られた。
    1)健全歯:窩洞の深さによる段階的な象牙芽細胞の変化、それに伴う樹枝状細胞の局在変化が観察された。深さ二分の一までは、著しい変化は見られないものの、それを越えると急激に変化が認められ、三分の二をこえると、象牙芽細胞が消失し代わりに樹枝状細胞が配列していた。
    2)う蝕歯:表層が再石灰化していると思われた平滑面エナメルう蝕下においても、樹枝状細胞ならび神経線維の集積がすでに観察され、象牙芽細胞の変化もみとめられ七他の免疫細胞の局在には変化は認められなかった。
    3)う蝕歯処置後:う蝕を除去した後でも局所的な樹枝状細胞、T細胞、神経線維の集積は認められ、深部う蝕ではB細胞も観察され、樹枝状細胞とリンパ球の頻繁な接合も認められた。画像解析による統計学的検討により、樹枝状細胞のう蝕前後の変化に有意差は認められなかった。しかしながら窩洞の深さによらず象牙芽細胞は常に認められ、健全歯で観察されたような樹枝状細胞による置換は認められなかった。
    全症例において、窩縁相当部には樹枝状細胞の集積は認められないことから、マイクロリーケージはおこっていないと考えられる。さらに、長期例、修復材料による組織反応の違いについて、検討中である。

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  • A study on mechanisms of odontoblast differentiation during reparative dentinogenesis.

    Grant number：10671789

    1998 - 2000

    System name：Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

    Research category：Grant-in-Aid for Scientific Research (C)

    Awarding organization：Japan Society for the Promotion of Science

    YOSHIBA Kunihiko, YOSHIBA Nagako, YAMAGA Masahiro

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    Grant amount：\3200000 （ Direct Cost: \3200000 ）

    In order to elucidate mechanisms by which pulp cells differentiate into odontoblasts during reparative dentinogenesis, immunohistochemical analyses for several factors related to cell differentiation were performed. The results were as follows :
    1. During tooth development, differential expression of laminin-5 and integrin α6 and β4 subunits in the inner dental epithelium may be involved in ameloblast differentiation. These changes in basement membrane composition might be also related to odontoblast differentiation.
    2. In pulps affected by early caries, MHC class II antigen-expressing cells (HLA-DR-positive dendritic cells) aggregated mainly in the cell-free zone associated with PGP 9.5-immuno-reactive nerve fibers. In advanced caries, the accumulated HLA-DR-positive cells and PGP 9.5-immunoreactive nerve fibers showed close association with each other especially beneath the odontoblast layer. Class II molecules were recognized not only in dendritic cells but also in the Schwann cells of non-myelinated nerves in the pulp. These suggested a synergistic action between immune and nervous systems in pulpal inflammation and reparative process.
    3. Pulpal responses after cavity preparation with either Er : YAG laser or a conventional drill were evaluated. The immunoreactivity for tissue non-specific alkaline phosphatase was more pronounced in the laser group. Clear similarities in the distribution patterns of OX6-immunopositive cells and PGP 9.5- immunoreactive nerve fibers were noted. OX6-positive MHC class II antigen-expressing cells accumulated along the pulp-dentin border and numerous bead-like PGP 9.5-immunoreactive nerve fibers were observed under the odontoblastic layer, suggesting their involvement in pulp tissue repair and reparative dentin formation.
    4. During hard tissue formation in the pulp cavity of rat molar after transplantation into subcutaneous tissue, non-collagenous proteins, such as osteocalcin, osteopontin, bone sialoprotein and dentin sialoprotein showed different distribution patterns in newly-formed hard tissues in the coronal, root canal and apex areas, respectively. These suggested that each hard tissue was formed by differently-derived cells.

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  • 生体親和性歯髄保護材の開発に関する基礎的研究

    Grant number：97J08780

    1998 - 1999

    System name：科学研究費助成事業 特別研究員奨励費

    Research category：特別研究員奨励費

    Awarding organization：日本学術振興会

    吉羽 永子

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    Grant amount：\2400000 （ Direct Cost: \2400000 ）

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  • 生体親和性材料に対する歯髄反応に関する研究

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    Grant type：Competitive

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  • 歯牙形成ならびに被蓋硬組織(dentin bridge)形成に関する研究

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    Grant type：Competitive

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  • 歯牙形成における上皮-間葉相互作用に関する研究

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    Grant type：Competitive

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  • Study on Pulpal Response to Biomaterials

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    Grant type：Competitive

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  • Study on tooth development and dentin bridge formation

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    Grant type：Competitive

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  • Epithelial-mesenchymal interactions during tooth development

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    Grant type：Competitive

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Teaching Experience

  • 口腔保健管理学特論

    2024
    Institution name：新潟大学

  • 健康福祉学入門

    2024
    Institution name：新潟大学

  • 生命医療科学総論

    2024
    Institution name：新潟大学

  • 一般口腔保健管理学I

    2024
    Institution name：新潟大学

  • 歯科臨床概論

    2024
    Institution name：新潟大学

  • 社会福祉原論II

    2024
    Institution name：新潟大学

  • 早期臨床実習IB

    2024
    Institution name：新潟大学

  • 歯科衛生学II

    2024
    Institution name：新潟大学

  • 高齢者福祉論II

    2024
    Institution name：新潟大学

  • 障害者福祉論II

    2024
    Institution name：新潟大学

  • 児童福祉論II

    2024
    Institution name：新潟大学

  • う蝕制御管理学演習IIA

    2022
    -
    2023
    Institution name：新潟大学

  • う蝕制御管理学演習IIB

    2022
    -
    2023
    Institution name：新潟大学

  • 歯科衛生士臨床実習II

    2021
    Institution name：新潟大学

  • 齲蝕学

    2020
    -
    2023
    Institution name：新潟大学

  • 生涯にわたる歯と咬合

    2019
    -
    2023
    Institution name：新潟大学

  • う蝕制御管理学演習ⅠA

    2017
    -
    2018
    Institution name：新潟大学

  • う蝕制御管理学演習ⅠB

    2017
    Institution name：新潟大学

  • エンドドンティックス

    2012
    -
    2013
    Institution name：新潟大学

  • 歯冠修復学

    2011
    -
    2014
    Institution name：新潟大学

  • 歯科診療補助Ⅱ

    2010
    Institution name：新潟大学

  • 統合科目Ⅱ

    2008
    -
    2019
    Institution name：新潟大学

  • 保存修復学実習

    2007
    -
    2023
    Institution name：新潟大学

  • う蝕学

    2007
    -
    2018
    Institution name：新潟大学

  • 保存修復学

    2007
    -
    2018
    Institution name：新潟大学

  • 歯内療法学実習

    2007
    -
    2009
    Institution name：新潟大学

  • 統合科目II

    2007
    Institution name：新潟大学

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