Updated on 2024/03/28

写真a

 
KISUPE Sarusedo Anhera
 
Organization
Academic Assembly Institute of Medicine and Dentistry SHIGAKU KEIRETU Assistant Professor
Graduate School of Medical and Dental Sciences Oral Life Science Tissue Regeneration and Reconstruction Assistant Professor
Title
Assistant Professor
Contact information
メールアドレス
Other name(s)
Angie
External link

Degree

  • 博士(歯学) ( 2014.9   新潟大学 )

Research Interests

  • Pulp Biology

  • Oral Histology

  • Tissue Regeneration

  • Tooth Development

  • Oral Anatomy

  • Gross Anatomy

  • Craniofacial Developmental Biology

Research Areas

  • Life Science / Regenerative dentistry and dental engineering

  • Life Science / Developmental dentistry

  • Life Science / Oral biological science

Research History

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

    2022.3

  • Niigata University   Tissue Regeneration and Reconstruction, Oral Life Science, Graduate School of Medical and Dental Sciences   Assistant Professor

    2022.3

Education

  • Niigata University   Faculty of Dentistry   PhD. in Oral Life Sciences

    2010.10 - 2014.9

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    Country: Japan

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  • Los Andes Private University   School of Stomatology   Master of Science in Stomatology

    2008.4 - 2010.3

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    Country: Peru

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  • National University of San Marcos   Faculty of Dentistry   DDS

    2001.4 - 2006.12

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    Country: Peru

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Professional Memberships

  • Japanese Association for Oral Biology (JAOB)

    2011

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  • The Japanese Association of Anatomists (JAA)

    2011

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  • International Association for Dental Research (IADR)

    2009

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Papers

  • Early revascularization activates quiescent dental pulp stem cells following tooth replantation in mice

    Hiroto Sano, Kuniko Nakakura-Ohshima, Angela Quispe-Salcedo, Yasuo Okada, Takuichi Sato, Hayato Ohshima

    Regenerative Therapy   24   582 - 591   2023.12

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

    DOI: 10.1016/j.reth.2023.10.004

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  • Actividad inhibitoria del extracto etanólico del Cyperus Rotundus procedente de la región de Cajamarca (provincia de Contumazá) en una cepa estandarizada de Streptococcus mutans (ATCC®25175)

    Rosita Belén Bazán Aliaga, Óscar Reátegui Arévalo, Luz Verónica Solórzano Espinoza, Juan Antonio Castro Arredondo, Víctor Elmo Miranda García, Elba Estefanía Martínez Cadillo, Angela Quispe-Salcedo

    Revista Científica Odontológica   10 ( 1 )   2022.4

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    Publishing type:Research paper (scientific journal)   Publisher:Universidad Cientifica del Sur  

    DOI: 10.21142/2523-2754-1001-2022-093

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  • The Critical Role of MMP13 in Regulating Tooth Development and Reactionary Dentinogenesis Repair Through the Wnt Signaling Pathway

    Henry F. Duncan, Yoshifumi Kobayashi, Yukako Yamauchi, Angela Quispe-Salcedo, Zhi Chao Feng, Jia Huang, Nicola C. Partridge, Teruyo Nakatani, Jeanine D’Armiento, Emi Shimizu

    Frontiers in Cell and Developmental Biology   10   2022.4

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    Matrix-metalloproteinase-13 (MMP13) is important for bone formation and remodeling; however, its role in tooth development remains unknown. To investigate this, MMP13-knockout (Mmp13−/−) mice were used to analyze phenotypic changes in the dentin–pulp complex, mineralization-associated marker-expression, and mechanistic interactions. Immunohistochemistry demonstrated high MMP13-expression in pulp-tissue, ameloblasts, odontoblasts, and dentin in developing WT-molars, which reduced in adults, with human-DPC cultures demonstrating a >2000-fold increase in Mmp13-expression during mineralization. Morphologically, Mmp13−/− molars displayed critical alterations in the dentin-phenotype, affecting dentin-tubule regularity, the odontoblast-palisade and predentin-definition with significantly reduced dentin volume (∼30% incisor; 13% molar), and enamel and dentin mineral-density. Reactionary-tertiary-dentin in response to injury was reduced at Mmp13−/− molar cusp-tips but with significantly more dystrophic pulpal mineralization in MMP13-null samples. Odontoblast differentiation-markers, nestin and DSP, reduced in expression after MMP13-loss in vivo, with reduced calcium deposition in MMP13-null DPC cultures. RNA-sequencing analysis of WT and Mmp13−/− pulp highlighted 5,020 transcripts to have significantly >2.0-fold change, with pathway-analysis indicating downregulation of the Wnt-signaling pathway, supported by reduced in vivo expression of the Wnt-responsive gene Axin2. Mmp13 interaction with Axin2 could be partly responsible for the loss of odontoblastic activity and alteration to the tooth phenotype and volume which is evident in this study. Overall, our novel findings indicate MMP13 as critical for tooth development and mineralization processes, highlighting mechanistic interaction with the Wnt-signaling pathway.

    DOI: 10.3389/fcell.2022.883266

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  • Exploration of the role of the subodontoblastic layer in odontoblast-like cell differentiation after tooth drilling using Nestin-enhanced green fluorescent protein transgenic mice

    Chihiro Imai, Hiroto Sano, Angela Quispe-Salcedo, Kotaro Saito, Mitsushiro Nakatomi, Hiroko Ida-Yonemochi, Hideyuki Okano, Hayato Ohshima

    Journal of Oral Biosciences   64 ( 1 )   77 - 84   2022.3

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    Objectives: Original odontoblasts and regenerated odontoblast-like cells (OBLCs) may differently regulate Nestin expression. This study aimed to investigate the role of the subodontoblastic layer (SOBL) using green fluorescent protein (GFP) reactivity in the process of OBLC differentiation after tooth drilling in Nestin-enhanced GFP transgenic mice. Methods: A groove-shaped cavity was prepared on the mesial surface of the maxillary first molars of 5- or 6-week-old mice under deep anesthesia. Immunohistochemical staining for Nestin and GFP and Nestin in situ hybridization were conducted on the sections obtained at 1–14 days postoperative. Results: Odontoblasts showed intense endogenous Nestin protein and mRNA expression, whereas the coronal SOBL cells showed a Nestin-GFP–positive reaction in the control groups. The injured odontoblasts had significantly decreased Nestin immunoreactivity as well as decreased expression of Nestin mRNA 1–2 days after the injury; subsequently, newly differentiated OBLCs were arranged along the pulp–dentin border, with significantly increased Nestin expression as well as increased expression of Nestin mRNA on days 3–5 to form reparative dentin. Nestin-GFP–positive cells at the pulp–dentin border significantly increased in number on days 1 and 2. GFP(+)/Nestin(+) and GFP(−)/Nestin(+) cells were intermingled in the newly differentiated OBLCs. Conclusions: The commitment of Nestin-GFP–positive cells into Nestin-positive OBLCs suggests that the restriction of endogenous Nestin protein and mRNA expression in the static SOBL cells was removed by exogenous stimuli, resulting in their migration along the pulp–dentin border and their differentiation into OBLCs.

    DOI: 10.1016/j.job.2022.01.001

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  • Grupos de investigación: juntos llegamos lejos

    Angela Quispe-Salcedo

    Revista Científica Odontológica   2021.10

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    DOI: 10.21142/2523-2754-0903-2021-066

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  • The effects of reducing the root length by apicoectomy on dental pulp revascularization following tooth replantation in mice

    Kuniko Nakakura-Ohshima, Angela Quispe-Salcedo, Hiroto Sano, Haruaki Hayasaki, Hayato Ohshima

    DENTAL TRAUMATOLOGY   37 ( 5 )   677 - 690   2021.10

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

    Background/Aim Root length is a critical factor for dental pulp regeneration following tooth replantation. The aim of this study was to analyze the effects of reducing the root length by apicoectomy on the pulp healing process using a model for tooth replantation.Material and Methods After extraction of the upper first molars (M1) of 3-week-old mice, the roots from the experimental group (EG) were shortened to half to two-thirds of their length before replantation, whereas in the control group (CG) the extracted teeth were immediately repositioned into their alveolar sockets. To determine the effects of root resection on the survival of inherent pulp cells, this study included tooth transplantation with root resection using wild-type (WT) and green fluorescent protein (GFP) transgenic mice. The M1 of GFP transgenic mice were transplanted into the alveolar socket of the M1 of WT mice. The roots of the right M1 were shortened (EG), whereas the left M1 remained untreated (CG).Results Apoptotic cells in the EG significantly decreased in number compared with the CG at day 3. Cell proliferative activity in the EG was significantly higher than that in the CG in the root pulp during days 3-5, and nestin-positive odontoblast-like cells began to arrange themselves along the pulp-dentin border in the cusp area at day 5 in the EG but not in the CG. At week 2, tertiary dentin had formed throughout the pulp in the EG, whereas the combined tissue of dentin and bone occupied the pulp space in 60% of the CG. Root resection also positively affected the survival of inherent pulp cells to differentiate into odontoblast-like cells as demonstrated by transplantation using GFP transgenic mice.Conclusions Reducing the root length accelerated pulp regeneration following tooth replantation due to the better environment for revascularization.

    DOI: 10.1111/edt.12679

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  • Ezh2 knockout in mesenchymal cells causes enamel hyper- mineralization

    Yoshifumi Kobayashi, Angela Quispe-Salcedo, Sanika Bodas, Satoko Matsumura, Erhao Li, Richard Johnson, Marwa Choudhury, Daniel H. Fine, Siva Nadimpalli, Henry F. Duncan, Amel Dudakovic, Andre J. van Wijnen, Emi Shimizu

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   567   72 - 78   2021.8

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:ACADEMIC PRESS INC ELSEVIER SCIENCE  

    Enhancer of zeste homolog 2 (EZH2) is the catalytic core of polycomb repressive complex 2 (PRC2), which primarily methylates lysine 27 on histone H3 (H2K27me3), generating transcriptionally suppressed heterochromatin. Since EZH2 suppresses expression of genes involved in dentin formation, we examined the role of EZH2 in tooth development. Intriguingly, microCT analysis of teeth from mice with conditional Ezh2 knockout in uncommitted mesenchymal cells showed hyper-mineralization of enamel, which is produced by the epithelial-lineage cells, ameloblasts. Scanning electron microscopy analysis and nano indentation of the incisor enamel from knockout mice revealed smaller inter-rod spaces and higher hardness compared to wild type enamel, respectively. Interestingly, expression of the calcium channel subunit gene, Orai2, was decreased compared to its competitor, Orai1, both in knockout mouse incisors and the ex vivo culture of ameloblasts with the surrounding tissues under EZH2 inhibition. Moreover, histological analysis of incisor from knockout mice showed decreased ameloblastin and expedited KLK4 expression in the ameloblasts. These observations suggest that EZH2 depletion in dental mesenchymal cells reduces enamel matrix formation and increases enamel protease activity from ameloblasts, resulting in enamel hyper-mineralization. This study demonstrates the significant role of the suppressive H3K27me3 mark for heterochromatin on enamel formation.& nbsp; (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

    DOI: 10.1016/j.bbrc.2021.06.003

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  • The Role of Dendritic Cells during Physiological and Pathological Dentinogenesis

    Angela Quispe-Salcedo, Hayato Ohshima

    JOURNAL OF CLINICAL MEDICINE   10 ( 15 )   2021.8

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    The dental pulp is a soft connective tissue of ectomesenchymal origin that harbors distinct cell populations, capable of interacting with each other to maintain the vitality of the tooth. After tooth injuries, a sequence of complex biological events takes place in the pulpal tissue to restore its homeostasis. The pulpal response begins with establishing an inflammatory reaction that leads to the formation of a matrix of reactionary or reparative dentin, according to the nature of the exogenous stimuli. Using several in vivo designs, antigen-presenting cells, including macrophages and dendritic cells (DCs), are identified in the pulpal tissue before tertiary dentin deposition under the afflicted area. However, the precise nature of this phenomenon and its relationship to inherent pulp cells are not yet clarified. This literature review aims to discuss the role of pulpal DCs and their relationship to progenitor/stem cells, odontoblasts or odontoblast-like cells, and other immunocompetent cells during physiological and pathological dentinogenesis. The concept of "dentin-pulp immunology" is proposed for understanding the crosstalk among these cell types after tooth injuries, and the possibility of immune-based therapies is introduced to accelerate pulpal healing after exogenous stimuli.

    DOI: 10.3390/jcm10153348

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  • An overview of Peruvian dental research in time of COVID-19

    Angela Quispe-Salcedo

    Revista Científica Odontológica   2020.12

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    DOI: 10.21142/2523-2754-0803-2020-027

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  • Responses of oral-microflora-exposed dental pulp to capping with a triple antibiotic paste or calcium hydroxide cement in mouse molars

    Angela Quispe-Salcedo, Takuichi Sato, Junko Matsuyama, Hiroko Ida-Yonemochi, Hayato Ohshima

    REGENERATIVE THERAPY   15   216 - 225   2020.12

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

    Introduction: Responses of oral-microflora-exposed dental pulp to a triple antibiotic paste (TAP), a mixture of ciprofloxacin, metronidazole, and minocycline in ointment with macrogol and propylene glycol, remain to be fully clarified at the cellular level. This study aimed to elucidate responses of oral-microflora-exposed dental pulp to capping with TAP in mouse molars.Methods: A cavity was prepared on the first molars of 6-week-old mice to expose the dental pulp for 24 h. The exposed pulp was capped with TAP (TAP group) or calcium hydroxide cement (CH group), in addition to the combination of macrogol (M) and propylene glycol (P) (MP, control group), followed by a glass ionomer cement filling. The samples were collected at intervals of 1, 2, and 3 weeks, and immunohistochemistry for nestin and Ki-67 and deoxyuride-5'-triphosphate biotin nick end labeling (TUNEL) assay were performed in addition to quantitative real-time polymerase chain reaction (qRT-PCR) analyses.Results: The highest occurrence rate of pulp necrosis was found in the control group followed by the CH group at Weeks 2 and 3, whereas the highest occurrence rate of healed areas in the dental pulp was observed in the TAP group at each time point. Tertiary dentin formation was first observed in the dental pulp of the TAP group at Week 2. In contrast, bone-like and/or fibrous tissues were frequently observed in the CH group. qRT-PCR analyses clarified that TAP activated the stem and dendritic cells at Weeks 1 and 2, respectively.Conclusions: The use of TAP as a pulp-capping agent improved the healing process of oral-microfloraexposed dental pulp in mouse molars. (C) 2020, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V.

    DOI: 10.1016/j.reth.2020.10.001

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  • Promotion of education and research in dental basic science. A call for action

    Vilma Chuquihuaccha-Granda, Angela Quispe-Salcedo

    Journal of Oral Research   9 ( 6 )   446 - 448   2020.11

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    DOI: 10.17126/joralres.2020.100

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  • COVID-19 y su impacto en la odontología peruana

    Angela Quispe-Salcedo

    Revista Científica Odontológica   8 ( 1 )   1 - 2   2020.4

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    Publishing type:Research paper (scientific journal)   Publisher:Universidad Cientifica del Sur  

    DOI: 10.21142/2523-2754-0801-2020-001

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  • Estudio in vitro del Efecto Antibacteriano de la Oleorresina de Copaifera reticulata y el Aceite Esencial de Origanum majoricum Frente a Streptococcus mutans y Enterococcus Faecalis Bacterias de Importancia en Patologías Orales

    Angela Quispe-Salcedo

    International journal of odontostomatology   2018.12

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    DOI: 10.4067/s0718-381x2018000400355

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  • La importancia de las ciencias básicas en la formación del cirujano dentista

    Angela Quispe-Salcedo

    Odontología Sanmarquina   2018.9

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    <jats:p>Explicar la ciencia no es tarea sencilla. Desde una aproximación actual, la ciencia puede definirse como una descripción sistemática de un determinado fenómeno presente en la naturaleza 1; donde la observación y la interpretación se interrelacionan para dar lugar a un nuevo conocimiento que se estandariza mediante el uso del método científico. Dentro de este contexto, la ciencia puede ser dividida en básica y aplicada, teniendo cada una características y objetivos distintos.</jats:p>

    DOI: 10.15381/os.v21i3.15145

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  • Nestin expression is differently regulated between odontoblasts and the subodontoblastic layer in mice

    Mitsushiro Nakatomi, Angela Quispe-Salcedo, Masaka Sakaguchi, Hiroko Ida-Yonemochi, Hideyuki Okano, Hayato Ohshima

    HISTOCHEMISTRY AND CELL BIOLOGY   149 ( 4 )   383 - 391   2018.4

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    The Nestin gene encodes type VI intermediate filament and is known to be expressed in undifferentiated cells during neurogenesis and myogenesis. To regulate Nestin expression, the first or second intron enhancer is activated in a tissue-dependent manner, for example, the former in mesodermal cells and the latter in neural stem cells. Although Nestin has also been used as a differentiation marker for odontoblasts during tooth development, how Nestin expression is regulated in odontoblasts remains unclear. Therefore, this study aimed to compare the expression patterns of Nestin-GFP (green fluorescent protein) with that of endogenous Nestin in developing teeth of Nestin-EGFP (enhanced GFP) transgenic mice, in which the second intron enhancer is connected with the EGFP domain, at postnatal 7d, 3w, and 8w. Immunohistochemical and in situ hybridization analyses revealed that endogenous Nestin protein and Nestin mRNA were intensely expressed in differentiated odontoblasts, while GFP immunoreactivity, which reflects the activity of Nestin second intron enhancer-mediated transcription, was mainly observed in the subodontoblastic layer. These results indicate that the first intron enhancer may be activated in differentiated odontoblasts. Intriguingly, Nestin-GFP expression in the subodontoblastic layer was found to be restricted to the coronal pulp of molars, which is susceptible to tooth injuries. Because the subodontoblastic layer serves as a reservoir of newly differentiated odontoblast-like cells upon exogenous stimuli to dentin, our findings suggest that the original odontoblasts and regenerated odontoblast-like cells may differently regulate Nestin expression.

    DOI: 10.1007/s00418-018-1651-3

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  • IGF-1 Mediates EphrinBl Activation in Regulating Tertiary Dentin Formation

    S. Matsumura, A. Quispe-Salcedo, C. M. Schiller, J. S. Shin, B. M. Locke, S. Yakar, E. Shimizu

    Journal of Dental Research   96 ( 10 )   1153 - 1161   2017.9

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    Eph receptors belong to a subfamily of receptor tyrosine kinases that are activated by membrane-spanning ligands called ephrins. Previously, we demonstrated that the ephrinB1-EphB2 interaction regulates odontogenic/osteogenic differentiation from dental pulp cells (DPCs) in vitro. The goal of this study was to identify the molecular mechanisms regulated by the EphB2/ephrinB1 system that govern tertiary dentin formation in vitro and in vivo. During tooth development, ephrinB1, and EphB2 were expressed in preodontoblast and odontoblasts at postnatal day 4. EphrinB1 was continuously expressed in odontoblasts and odontoblastic processes until the completion of tooth eruption. In addition, ephrinB1 was expressed in odontoblastic processes 2 wk following tooth injury without pulp exposure, whereas EphB2 was expressed in the center of pulp niches but not odontoblasts. In a model of tooth injury with pulp exposure, ephrinB1 was strongly expressed in odontoblasts 4 wk postinjury. In vitro studies with human and mouse DPCs treated with calcium hydroxide (CH) or mineral trioxide aggregate (MTA) showed an increased expression of insulin-like growth factor 1 (IGF-1). Experiments using several inhibitors of IGF-1 receptor signaling revealed that inhibiting the Ras/Raf-1/MAPK pathway inhibited EphB2 expression, and inhibiting the PI3K/Akt/mTOR pathway specifically inhibited ephrinB1 gene expression. Tooth injury in mice with odontoblast-specific IGF-1 receptor ablation exhibited a reduced tertiary dentin volume, mineral density, and ephrinB1 expression 4 wk following injury. We conclude that the IGF-1/ephrinB1 axis plays significant roles in the early stages of tooth injury. Further research is needed to fully understand the potential of targeting ephrinB1 as a regenerative pulp therapy.

    DOI: 10.1177/0022034517708572

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  • Intercellular Genetic Interaction Between Irf6 and Twist1 during Craniofacial Development

    Walid D. Fakhouri, Kareem Metwalli, Ali Naji, Sarah Bakhiet, Angela Quispe-Salcedo, Larissa Nitschke, Youssef A. Kousa, Brian C. Schutte

    SCIENTIFIC REPORTS   7   2017.8

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    Interferon Regulatory Factor 6 (IRF6) and TWIST1 are transcription factors necessary for craniofacial development. Human genetic studies showed that mutations in IRF6 lead to cleft lip and palate and mandibular abnormalities. In the mouse, we found that loss of Irf6 causes craniosynostosis and mandibular hypoplasia. Similarly, mutations in TWIST1 cause craniosynostosis, mandibular hypoplasia and cleft palate. Based on this phenotypic overlap, we asked if Irf6 and Twist1 interact genetically during craniofacial formation. While single heterozygous mice are normal, double heterozygous embryos (Irf6(+/-); Twist1(+/-)) can have severe mandibular hypoplasia that leads to agnathia and cleft palate at birth. Analysis of spatiotemporal expression showed that Irf6 and Twist1 are found in different cell types. Consistent with the intercellular interaction, we found reduced expression of Endothelin1 (EDN1) in mandible and transcription factors that are critical for mandibular patterning including DLX5, DLX6 and HAND2, were also reduced in mesenchymal cells. Treatment of mandibular explants with exogenous EDN1 peptides partially rescued abnormalities in Meckel's cartilage. In addition, partial rescue was observed when double heterozygous embryos also carried a null allele of p53. Considering that variants in IRF6 and TWIST1 contribute to human craniofacial defects, this gene-gene interaction may have implications on craniofacial disorders.

    DOI: 10.1038/s41598-017-06310-z

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  • The effects of enzymatically synthesized glycogen on the pulpal healing process of extracted teeth following intentionally delayed replantation in mice

    Angela Quispe-Salcedo, Hiroko Ida-Yonemochi, Hayato Ohshima

    JOURNAL OF ORAL BIOSCIENCES   57 ( 2 )   124 - 130   2015.5

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    Objectives: Glucose uptake plays a crucial role in early tooth morphogenesis and size determination. Recently, enzymatically synthesized glycogen (ESG), with the characteristics of natural glycogen (a major storage form of glucose), has been developed. This study aimed to elucidate the effectiveness of ESG on the pulpal healing process following intentionally delayed tooth replantation in mice.Methods: The upper first molar was extracted, immersed in phosphate buffered saline (PBS) or ESG (5000 kDa) solution (1 mg/mL) for 60 min, and then replanted. Immunohistochemistry (for nestin, osteopontin, and TUNEL assay, and reverse transcription-polymerase chain reaction were performed at different time points.Results: Increased apoptosis occurred in the dental pulp of mice from both treatment groups at Day 7, followed by active cell proliferation at Day 14 and tertiary dentin and/or bone-like tissue deposition at Day 21, in the PBS group. In contrast, active cell proliferation and coronal immunoreaction for nestin occurred around Day 10, and hard tissue deposition were observed at Day 14, in the ESG group. The mRNA expression of genes encoding dentin sialophosphoprotein and nestin first reappeared in the ESG group at Day 5, while expression levels of alkaline phosphatase and osteopontin, as well as Crillc, tended to increase from Day 3 in both groups, and that of the stem cell marker, octamer-binding transcription factor Oct314, greatly enhanced at Day 1, particularly in the ESG group.Conclusions: ESG improved the pulpal healing process of extracted teeth following intentionally delayed replantation, although both ESG and PBS may induce the formation of bone-like tissue. (C) 2015 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.job.2015.01.003

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  • Effects of a Triple Antibiotic Solution on Pulpal Dynamics after Intentionally Delayed Tooth Replantation in Mice

    Angela Quispe-Salcedo, Hiroko Ida-Yonemochi, Hayato Ohshima

    JOURNAL OF ENDODONTICS   40 ( 10 )   1566 - 1572   2014.10

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    Introduction:. This study analyzed the detailed biological events underlying pulpal dynamics evoked by 3Mix (the mixture of ciprofloxacin, metronidazole, and minocycline) solution after intentionally delayed tooth replantation because 3Mix improves pulpal healing after tooth injuries. Methods: The maxillary first molars of 3-week-old mice were extracted and immersed in 3Mix solution for 30 minutes in comparison with phosphate buffered saline (PBS) alone. Cell proliferation, apoptosis, and differentiation were assessed in extracted/replanted teeth during days 0-14 using immunohistochemistry, apoptosis assay, and reverse-transcriptase polymerase chain reaction. Results: 3Mix solution accelerated odontoblast differentiation in the coronal pulp on day 7 and tertiary dentin formation on day 14, whereas the regenerative process was delayed in the PBS group. Cell proliferation and apoptosis occurred in the pulp of the 3Mix group during days 5-7 and subsequently decreased from days 7-14. On day 5, dentin sialophosphoprotein and nestin were first recovered in the 3Mix group, whereas expression levels for alkaline phosphatase, osteopontin, and osteocalcin increased in the PBS group. The expression levels for octamer-binding factor 3/4A and 3/4B reached the maximum level on day 1 and were sharply decreased on day 3 in both groups. High expression levels of Cd11c were first observed in the 3Mix group on day 1 and later at days 5 and 7. Conclusions: The results suggest that the application of 3Mix may suppress osteoblast differentiation by the migration of dendritic cells to the injury site and via the activation of stem/progenitor cells, resulting in the acceleration of odontoblastlike cell differentiation.

    DOI: 10.1016/j.joen.2014.05.005

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  • Use of a triple antibiotic solution affects the healing process of intentionally delayed replanted teeth in mice

    Angela Quispe-Salcedo, Hiroko Ida-Yonemochi, Hayato Ohshima

    JOURNAL OF ORAL BIOSCIENCES   55 ( 2 )   91 - 100   2013.5

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    <bold>Objective: </bold>A mixture of ciprofloxacin, metronidazole, and minocycline (3Mix) has been reported to be effective against oral bacteria from carious and endodontic lesions in vitro and in vivo. The objective of this study was to establish an animal model using mice for the application of 3Mix following intentionally delayed tooth replantation and to investigate the effects of 3Mix on the healing process of dental pulp and periodontal tissues. <bold> </bold>Methods<bold>: </bold>Upper first molars of ICR mice were extracted, immersed in 3Mix solution at different concentrations for 560 min with or without the use of a transfer solution (phosphate buffer solution (PBS)), in addition to transfer solution alone, and subsequently repositioned in the sockets. Immunohistochemistry for nestin and Ki-67, histochemistry for TRAP, and TUNEL assay were performed to assess pulpal healing during days 721. <bold> </bold>Results<bold>: </bold>Increased apoptosis was observed in the PBS group at week 1, followed by cell proliferation at week 2, and tertiary dentin and/or bone-like tissue formation at week 3. In contrast, nestin-positive, newly differentiated, odontoblast-like cells began to align along the pulpdentin border following the appearance of Ki-67- and TUNEL-positive cells during weeks 12 in the 3Mix groups, suggesting that pulpal healing was accelerated. Severe root ankylosis was observed exclusively in the 3Mix groups. Rinsing with PBS before replantation partially rescued the viability of the periodontal ligament, but pulpal healing was delayed. <bold> </bold>Conclusions<bold>:</bold>The application of 3Mix promotes pulpal regeneration of intentionally delayed replanted teeth; however, its use may induce severe damage to periodontal tissues. (C) 2013 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.

    DOI: 10.1016/j.job.2013.03.001

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  • Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

    Angela Quispe-Salcedo, Hiroko Ida-Yonemochi, Mitsushiro Nakatomi, Hayato Ohshima

    BIOMEDICAL RESEARCH-TOKYO   33 ( 2 )   119 - 132   2012.4

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    Language:English   Publishing type:Research paper (scientific journal)   Publisher:BIOMEDICAL RESEARCH PRESS LTD  

    Differentiated odontoblasts could not be identified by one unique phenotypic marker, but the combination of expression of dentin phosphoprotein (Dpp), dentin sialoprotein (Dsp), dentin matrix protein 1 (Dmp1), and nestin may be valuable for the assessment of these cells. However, the findings using these proteins remain controversial. This study aimed to compare two odontoblast differentiation markers: nestin and Dsp in the process of dentinogenesis in mice. We performed immunohistochemistry and/or in situ hybridization technique for nestin and Dsp using 3-week-old incisors as well as postnatal 1-day- to 8-week-old molars. Preodontoblasts began to express nestin and Dsp proteins and Dsp mRNA, which increased in their intensity according to the progress of odontoblast differentiation in both incisors and developing molars. Nestin was consistently expressed in the differentiated odontoblasts even after the completion of dentin matrix deposition. The expression of Dsp mRNA coincided with the odontoblast secretory activity for dentin matrix deposition. In contrast, other pulpal cells, predentin matrix and dentinal tubules also showed a positive reaction for Dsp protein in addition to differentiated odontoblasts. In conclusion, nestin is valuable as a differentiation marker for odontoblasts, whereas Dsp mRNA is a functional marker for their secretory activity.

    DOI: 10.2220/biomedres.33.119

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Research Projects

  • Homeostatic maintenance and activation of dental pulp quiescent stem/progenitor cells regulated by dendritic cells and macrophages

    Grant number:23H03078

    2023.4 - 2026.3

    System name:Grants-in-Aid for Scientific Research

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

    Awarding organization:Japan Society for the Promotion of Science

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    Grant amount:\18980000 ( Direct Cost: \14600000 、 Indirect Cost:\4380000 )

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Teaching Experience (researchmap)

  • Gross Anatomy

    2021.6
    Institution name:Niigata University, Faculty of Dentistry

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  • General and Oral Embryology

    2018
    -
    2021
    Institution name:Cientifica del Sur University (Lima, Peru)

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  • General and Oral Histology

    2018
    -
    2021
    Institution name:Cientifica del Sur University (Lima, Peru)

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Teaching Experience

  • 人体解剖学I

    2023
    Institution name:新潟大学

  • 人体解剖学実習

    2023
    Institution name:新潟大学

  • 人体解剖学II

    2023
    Institution name:新潟大学