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

DOI： 10.1016/j.oooo.2022.07.007

researchmap

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

DOI： 10.1016/j.adoms.2021.100157

researchmap

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

DOI： 10.1016/j.adoms.2021.100166

researchmap

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

DOI： 10.1016/j.adoms.2021.100081

researchmap

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

The oxygen concentration in normal human tissue under physiologic conditions is lower than the atmospheric oxygen concentration. The more hypoxic condition has been observed in the cells with wound healing and cancer. Somatic stem cells reside in a hypoxic microenvironment in vivo and prefer hypoxic culture conditions in vitro. Oral mucosa contains tissue-specific stem cells, which is an excellent tissue source for regenerative medicine. For clinical usage, maintaining the stem cell in cultured cells is important. We previously reported that hypoxic culture conditions maintained primary oral keratinocytes in an undifferentiated and quiescent state and enhanced their clonogenicity. However, the metabolic mechanism of these cells is unclear. Stem cell biological and pathological findings have shown that metabolic reprogramming is important in hypoxic culture conditions, but there has been no report on oral mucosal keratinocytes and fibroblasts. Herein, we conducted metabolomic analyses of oral mucosal keratinocytes and fibroblasts under hypoxic conditions. Hypoxic oral keratinocytes and fibroblasts showed a drastic change of metabolite concentrations in urea cycle metabolites and polyamine pathways. The changes of metabolic profiles in glycolysis and the pentose phosphate pathway under hypoxic conditions in the oral keratinocytes were consistent with those of other somatic stem cells. The metabolic profiles in oral fibroblasts showed only little changes in any pathway under hypoxia except for a significant increase in the antioxidant 2-oxoglutaric acid. This report firstly provides the holistic changes of various metabolic pathways of hypoxic cultured oral keratinocytes and fibroblasts.

DOI： 10.3390/jcm10061156

PubMed

researchmap

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

Condylar resorption (CR) after surgical orthognathic treatment is defined as dysfunctional remodeling of the temporomandibular joint manifested by morphological changes with decreased condylar head volume that cause occlusal and esthetic changes. Although both conservative and surgical treatment strategies have been employed for the treatment of CR, effective procedures have not been established till date. In this study, the effects of MSC-CM on CR were investigated. Bone marrow-derived MSCs of rats (rMSCs) were cultured until 80% confluent, cultured in serum-free conditioned medium for 48 h; the collected medium was defined as MSC-CM. Osteogenesis, chondrogenesis, and angiogenesis-related gene expression in rMSCs cultured with MSC-CM was evaluated by quantitative real-time polymerase chain reaction. A rat CR model was used for animal studies, in which CR occurred after mandibular distraction osteogenesis for 10 days. MSC-CM was injected via the tail vein and quantitative and qualitative evaluations were performed by micro-computed tomography (micro-CT) and histology. MSC-CM enhanced osteogenesis-, chondrogenesis-, and angiogenesis-related gene expression in rMSCs. Micro-CT showed CR in control groups; however, it was observed to be improved in the MSC-CM group. Histologically, an enlarged cartilage layer was seen in the MSC-CM group, while cartilage layers had almost thinned or disappeared in control groups. These results indicate that MSC-CM improved CR.

DOI： 10.1016/j.heliyon.2021.e06530

PubMed

researchmap

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

Objective: To evaluate oral health-related quality of life (OHRQoL) in patients with temporomandibular disorders (TMDs).Methods: Subjects included 56 patients diagnosed with TMD. Control subjects consisted of 30 individuals without temporomandibular joint symptoms. OHRQoL was evaluated using the Japanese version of the Oral Health Impact Profile (OHIP-J54) before and 4 months after treatment.Results: Total score and all subscale scores of the OHIP-J54 in patients before treatment were significantly higher than those of the control subjects and were significantly improved after treatment, except for social disability. Gender and NRS pain scores had statistically significant effects on OHRQoL, which was low in females and patients with severe pain.Conclusion: OHIP-J54 appeared to be useful for understanding psychological and social problems as a screening tool and for assessing the extent of changes in the well-being of patients with TMD.

DOI： 10.1080/08869634.2021.1883378

PubMed

researchmap

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

Background/purpose: Conditioned media of cultured mesenchymal stem cells (MSCs) contain numerous kinds of secretomes such as cytokines and chemokines. We previously reported that conditioned media of bone marrow-derived MSCs (MSC-CM) promote bone formation. Recently, macrophage phenotype switching from the pro-inflammatory M1 type to the anti-inflammatory M2 type has been reported to be an important phenomenon during tissue regeneration. Some studies reported that this phenotype switching is regulated by secretomes. In this study, macrophage phenotype during bone formation by MSC-CM was investigated. Materials and methods: Human MSCs (hMSCs) were cultured in serum-free medium and the collected medium was defined as MSC-CM. Macrophage-related gene expressions in hMSCs cultured with MSC-CM were evaluated by quantitative real-time polymerase chain reaction. MSC-CM was implanted and the evaluations by micro-CT and immunohistochemistry were performed using a rat the calvaria bone defect model. Results: Two and four weeks after implantation, the MSC-CM group demonstrated enhanced bone regeneration. Gene expressions of C–C motif chemokine 2 (CCL2), colony-stimulating factor 2 (CSF2) and CD163 was significantly upregulated in cells exposed to MSC-CM. Immunohistochemical staining revealed that iNOS-positive M1 macrophages were reduced, while CD204-positive M2 macrophages were increased in the MSC-CM group at 72 h after implantation, and the M2/M1 ratio increased only in the MSC-CM group. Conclusion: MSC-CM enhances macrophage migration and induces M1 to M2 type macrophage switching at an early stage of osteogenesis. Such phenotype switching provides a favorable environment for angiogenesis, cellular migration, and osteogenesis and contributes to MSC-CM-induced early bone formation.

DOI： 10.1016/j.jds.2021.08.012

Scopus

researchmap

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

The differences between oral mucosa and skin wound healing involving hypoxic responses of fibroblasts are poorly elucidated. In this study, we aimed to study the different hypoxic responses between oral and skin fibroblasts embedded in a three-dimensional (3D) collagen matrix to address the early stage of wound healing. Primary oral mucosa fibroblasts (OMFs) obtained from the retromolar area and skin fibroblasts (SFs) obtained from the abdomen were cultured in the 3D 'floating model' under either 21%, 5% or 1% O2 for 2 days. Cell viability under hypoxia was higher in the OMFs than in the SFs. Collagen gel contraction was suppressed under hypoxic conditions in both fibroblasts, consistent with the reduction of alpha smooth muscle actin expression, except for SFs under 1% O2. Subsequently, their gene expression profiles between 21 and 1% O2 concentrations were compared via microarray technology, and the expression profiles of the extracellular matrix (ECM)-associated proteins, including matrix metalloproteinases and collagens, were evaluated. The OMFs were more susceptible to 1% O2, and more of their genes were downregulated than the SFs'. Although the production and expression levels of ECM-associated proteins in both fibroblasts diminished under hypoxia, those levels in OMFs were significantly higher than those in SFs. In the case of single origin OMFs and SFs, our findings suggest that OMFs possess a higher baseline production capacity of several ECM-associated proteins than SFs, except type III collagen. The intrinsic hypoxic responses of OMFs may be attributed to a more favourable wound healing in oral mucosa.

DOI： 10.1007/s11626-020-00458-1

PubMed

researchmap

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

© 2020 Asian AOMS(+) ASOMP(+) JSOP(+) JSOMS(+) JSOM(+) and JAMI Venous thromboembolism (VTE) is a potential life-threatening complication after major surgery. We report two patients in whom VTE occurred during surgical orthodontic treatment for jaw deformities and who underwent orthognathic surgery with VTE recurrence prevention measures. The first patient was a 31-year-old female. She complained of pain in her left lower leg three days after bilateral sagittal split osteotomies and was diagnosed with deep vein thrombosis (DVT) by ultrasonography. Anticoagulant therapy with warfarin potassium was performed for four months after surgery, and the DVT was not observed by ultrasonography. One year after the first surgery, reduction genioplasty was performed with fondaparinux sodium administration as the highest risk case of VTE. The second patient was a 34-year-old male. He was diagnosed with pulmonary embolism (PE) and lower limb DVT during preoperative orthodontic treatment. The patient received anticoagulant therapy with danaparoid sodium and warfarin potassium under hospitalization for two weeks, and anticoagulant therapy with warfarin potassium was continued for six months. Ten months after VTE onset, orthognathic surgeries were performed with heparin calcium administration as the highest risk case of VTE. Patients undergoing orthognathic surgery have a low risk of VTE, but attention should be paid to clinical symptoms such as local swelling, redness, calf muscle tenderness, difficulty in breathing and chest pain after surgery. In addition, if the patient has a history of VTE, anticoagulant therapy after orthognathic surgery must be added to the standard preventive measures for VTE.

DOI： 10.1016/j.ajoms.2020.06.011

Scopus

researchmap

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

researchmap

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

Background: The free vascularized fibula flap presents many advantages such as sufficient length of the bony segment, good vascularization, better quality of the bone, and a long vascular pedicle, but it is also associated with some disadvantages with regard to prosthetic rehabilitation because of its limited height. Improvement in bone height is necessary for ideal dental implant treatment of reconstructed mandibles. Case presentation: For two squamous cell carcinoma patients, mandibular bone reconstruction was performed secondarily with the peroneal flap after tumor resection. Since the bone height was insufficient at the time of implant treatment, occlusion reconstruction by dental implant was performed after vertical distraction osteogenesis. Conclusions: Vertical distraction osteogenesis is a suitable treatment option for alveolar ridge deficiency resulting from fibula transplantation for mandibular reconstruction following tumor surgery.

DOI： 10.1186/s40902-018-0172-2

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer-Verlag Italia s.r.l.  

DOI： 10.1007/s10072-018-3436-9

Scopus

PubMed

researchmap

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

Periodic patterning of iterative structures is diverse across the animal kingdom. Clarifying the molecular mechanisms involved in the formation of these structure helps to elucidate the process of organogenesis. Turing-type reaction-diffusion mechanisms have been shown to play a critical role in regulating periodic patterning in organogenesis. Palatal rugae are periodically patterned ridges situated on the hard palate of mammals. We have previously shown that the palatal rugae develop by a Turing-type reaction-diffusion mechanism, which is reliant upon Shh (as an inhibitor) and Fgf (as an activator) signaling for appropriate organization of these structures. The disturbance of Shh and Fgf signaling lead to disorganized palatal rugae. However, the mechanism itself is not fully understood. Here we found that Lrp4 (transmembrane protein) was expressed in a complementary pattern to Wise (a secreted BMP antagonist and Wnt modulator) expression in palatal rugae development, representing Lrp4 expression in developing rugae and Wise in the inter-rugal epithelium. Highly disorganized palatal rugae was observed in both Wise and Lrp4 mutant mice, and these mutants also showed the downregulation of Shh signaling, which was accompanied with upregulation of Fgf signaling. Wise and Lrp4 are thus likely to control palatal rugae development by regulating reaction-diffusion mechanisms through Shh and Fgf signaling. We also found that Bmp and Wnt signaling were partially involved in this mechanism.

DOI： 10.1371/journal.pone.0204126

PubMed

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Identifying substandard tissue-engineered oral mucosa grafts with a poor epithelium before clinical use is critical to ensure quality assurance/control in regenerative medicine, leading to success of grafting. This study investigated the effects of one of the C-xylopyranoside derivatives, β-D-xylopyranoside-n-propane-2-one (XPP), on oral epithelial regeneration. Using a three-dimensional oral mucosa model, we analyzed changes of the epithelial structure, glycosaminoglycan (GAG) synthesis, the expression levels of basement membrane zone markers, and substrates of Akt/mTOR signaling. Compared with the control, 2 mM XPP treatment increased the mean and minimal epithelial thickness, and reduced the variation of epithelial thickness. It also stimulated expressions of decorin and syndecan-1 with change of GAG amount and/or composition, and enhanced the expressions of integrin α6, CD44, and Akt/mTOR signaling substrates. These findings suggest that XPP supplementation contributes to consistent epithelial regeneration. Moreover, upregulation of those markers may play a role in increasing the quality of the oral mucosal epithelium.

DOI： 10.1080/09168451.2016.1153957

Web of Science

PubMed

researchmap

Publishing type：Doctoral thesis  

researchmap

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

Denture-wearing affects the quality and quantity of epithelial cells in the underlying healthy oral mucosa. The physiologic mechanisms, however, are poorly understood. This study aimed to compare histologic changes and cellular responses of an epithelial cell layer to cyclic mechanical pressure-loading mimicking denture-wearing using an organotypic culture system to develop a three-dimensional in vitro oral mucosa model (3DOMM). Primary human oral keratinocytes and fibroblasts were serially grown in a monolayer culture, and cell viability was measured under continuous cyclic mechanical pressure (50kPa) for 7days (cycles of 60min on, 20s off to degas and inject air). Upon initiation of an air-liquid interface culture for epithelial stratification, the cyclic pressure, set to the mode above mentioned, was applied to the 3DOMMs for 7days. Paraffin-embedded 3DOMMs were examined histologically and immunohistochemically. In the monolayer culture, the pressure did not affect the viability of oral keratinocytes or fibroblasts. Few histologic changes were observed in the epithelial layer of the control and pressure-loaded 3DOMMs. Immunohistochemical examination, however, revealed a significant decrease in Ki-67 labelling and an increase in filaggrin and involucrin expression in the suprabasal layer of the pressure-loaded 3DOMMs. Pressure-loading attenuated integrin 1 expression and increased matrix metalloproteinase-9 activity. Incomplete deposition of laminin and type IV collagen beneath the basal cells was observed only in the pressure-loaded 3DOMM. Cyclic pressure-loading appeared to disrupt multiple functions of the basal cells in the 3DOMM, resulting in a predisposition towards terminal differentiation. Thus, denture-wearing could compromise oral epithelial homeostasis.

DOI： 10.1111/joor.12254

Web of Science

PubMed

researchmap

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

We have histologically examined vascular invasion and calcification of the hypertrophic zone during endochondral ossification in matrix metalloproteinase (MMP)-9 deficient (MMP-9-/-) mice and in their littermates at 3 days, 3 weeks and 6 weeks after birth. Capillaries and osteoclasts at the chondro-osseous junction showed an intense MMP-9 immunopositivity, suggesting that they recognize chemical properties of cartilaginous matrices, and then release MMP-9 for cartilage degradation. CD31-positive capillaries and tartrate-resistant acid phosphatase-reactive osteoclasts could be found in the close proximity in the region of chondro-osseous junction in MMP-9-/- mice, while in wild-type mice, vascular invasion preceded osteoclastic migration into the epiphyseal cartilage. Although MMP-9-/- mice revealed larger hypertrophic zones, the index of calcified area was significantly smaller in MMP-9-/- mice. Interestingly, the lower layer of the MMP-9-/- hypertrophic zone showed intense MMP-13 staining, which could not be observed in wild-type mice. This indicates that MMP-13 may compensate for MMP-9 deficiency at that specific region, but not to a point at which the deficiency could be completely rescued. In conclusion, it seems that MMP-9 is the optimal enzyme for cartilage degradation during endochondral ossification by controlling vascular invasion and subsequent osteoclastic migration.

DOI： 10.2220/biomedres.34.119

Web of Science

PubMed

researchmap

Authorship：Lead author,　Corresponding author   Language：Japanese   Publishing type：Research paper (scientific journal)  

J-GLOBAL

researchmap

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

A replacement of proline with leucine at position 132 of the receptor for parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP), i.e., PTH-R, has been discovered in human Blomstrand's lethal chondrodysplasia. As skeletal deformities in this type of chondrodysplasia appear to compromise the receptor binding to its ligands, we examined the possibility that rat PTH-R carrying P132L mutation (PTH-R(P132L)) would result in abnormal intracellular localization. Osteoblastic MC3T3-E1 cells were transfected with expression vectors containing cDNAs encoding either wild-type PTH-R or mutant PTH-R(P132L). The cells expressing the wild-type PTH-R produced a receptor protein with a molecular mass of 66.3 kDa, which localized its immunoreactivity mainly on the cell surfaces. In contrast, the PTH-R(P132L) was hardly detected on the cell surfaces, but accumulated within the rough-surfaced endoplasmic reticulum. Consistent with this localization, the cells expressing the mutant receptor failed to generate cyclic AMP in response to PTH. Furthermore, a remarkably weaker intensity of the 66.3 kDa band compared with the wild-type counterpart suggests that PTH-R(P132L) is prone to degradation in the transfected cells. In summary, these findings indicate that defective transport of PTH-R(P132L) to the cell surface would be a molecular basis for Blomstrand's chondrodysplasia.

DOI： 10.2220/biomedres.29.61

Web of Science

PubMed

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

J-GLOBAL

researchmap

J-GLOBAL

researchmap

Language：Japanese   Publisher：(一社)日本形成外科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

researchmap

Language：Japanese   Publisher：(一社)日本形成外科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：日本口腔顎顔面外傷学会  

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本顎変形症学会  

researchmap

Language：Japanese   Publisher：新潟歯学会  

顎口腔領域の転移性腫瘍は稀である。われわれは、上顎歯肉へ転移した腎細胞癌の1例を経験したのでその概要を報告する。患者は74歳の男性で、上顎左側歯肉の腫脹を主訴に開業歯科を受診し、切開排膿処置を受けたところ止血困難となり当科を受診した。既往歴に腎細胞癌があり、分子標的薬による加療が行われていたが、副作用のため腫脹を自覚する1ヵ月程前より中止となっていた。臨床所見では、上顎左側大臼歯部歯肉に弾性軟、表面平滑で無痛性の20×10mmの腫瘤を認めた。CTでは上顎左側大臼歯部に長径22mmの類球形の腫瘤性病変を認め、周囲の骨吸収を伴っていた。試験切除を施行し、病理組織学的に淡明細胞型腎細胞癌の診断を得た。分子標的薬を再開したところ腫瘍は縮小した。経過観察期間中、口腔内転移腫瘍は分子標的薬に反応を示したが、多発肝転移、多発膵転移、両側副腎転移、多発胆嚢転移、腹部播種をきたし、当科初診から4年3ヵ月、初発から16年後に死の転帰をたどった。(著者抄録)

researchmap

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：日本再生歯科医学会  

researchmap

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(公社)日本顎顔面インプラント学会  

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese   Publisher：日本骨形態計測学会  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(株)医薬ジャーナル社  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese   Publisher：(NPO)日本口腔科学会  

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese   Publisher：新潟歯学会  

researchmap

Language：Japanese   Publisher：(一社)日本形成外科学会  

researchmap

Language：Japanese   Publisher：日本再生歯科医学会  

researchmap

Language：Japanese   Publisher：(一社)日本解剖学会  

researchmap

Language：English   Publisher：日本骨形態計測学会  

researchmap

Language：Japanese   Publisher：(一社)日本解剖学会  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese  

J-GLOBAL

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：English   Presentation type：Oral presentation (general)  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：Japanese  

researchmap

Language：English  

researchmap

Language：Japanese  

researchmap