Authorship：Last author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

The pathology of medication-related osteonecrosis of the jaw (MRONJ), often associated with antiresorptive therapy, is still not fully understood. Osteocyte networks are known to play a critical role in maintaining bone homeostasis and repair, but the exact condition of these networks in MRONJ is unknown. On the other hand, the local application of E-coli-derived Recombinant Human Bone Morphogenetic Protein 2/β-Tricalcium phosphate (E-rhBMP-2/β-TCP) has been shown to promote bone regeneration and mitigate osteonecrosis in MRONJ-like mouse models, indicating its potential therapeutic application for the treatment of MRONJ. However, the detailed effect of BMP-2 treatment on restoring bone integrity, including its osteocyte network, in an MRONJ condition remains unclear. Therefore, in the present study, by applying a scanning electron microscope (SEM) analysis and a 3D osteocyte network reconstruction workflow on the alveolar bone surrounding the tooth extraction socket of an MRONJ-like mouse model, we examined the effectiveness of BMP-2/β-TCP therapy on the alleviation of MRONJ-related bone necrosis with a particular focus on the osteocyte network and alveolar bone microstructure (microcrack accumulation). The 3D osteocyte dendritic analysis showed a significant decrease in osteocyte dendritic parameters along with a delay in bone remodeling in the MRONJ group compared to the healthy counterpart. The SEM analysis also revealed a notable increase in the number of microcracks in the alveolar bone surface in the MRONJ group compared to the healthy group. In contrast, all of those parameters were restored in the E-rhBMP-2/β-TCP-treated group to levels that were almost similar to those in the healthy group. In summary, our study reveals that MRONJ induces osteocyte network degradation and microcrack accumulation, while application of E-rhBMP-2/β-TCP can restore a compromised osteocyte network and abrogate microcrack accumulation in MRONJ.

DOI： 10.3390/ijms25126648

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

DOI： 10.1016/j.joca.2024.06.009

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Language：Japanese   Publisher：(一社)日本老年歯科医学会  

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

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial–mesenchymal cell co-culture models in the air–liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.

DOI： 10.3390/cells13100807

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Language：Japanese   Publisher：(一社)日本デジタル歯科学会  

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

Objective

This systematic review aimed to provide an overview of the most recent evidence on the association between measured masticatory function and cognitive status.

Materials and Methods

Literature and manual searches were conducted using three electronic databases (PubMed, Web of Science and CINAHL). Observational studies published between 2011 and 2021 investigating the association between masticatory function, dementia and cognitive status in adult humans were abstracted and reviewed by three reviewers. Studies that assessed participants' masticatory function using objective and subjective measurements and that individually examined its association with cognitive function were included. The included studies were divided into cross‐sectional and cohort studies, and the quality of each study was analysed using critical appraisal skills checklists. Additionally, the main conclusions and strength of the evidence were assessed for each article.

Results

A total of 21 studies (11 cross‐sectional studies that objectively evaluated masticatory function, 9 cross‐sectional studies that subjectively evaluated masticatory function and 1 prospective cohort study) were evaluated. The poorer masticatory function was associated with lower cognitive status even after adjusting for potential risk factors of dementia in four of 11 and six of nine cross‐sectional studies where the masticatory function was respectively evaluated objectively and subjectively. One prospective cohort study also demonstrated that masticatory function, as evaluated based on measurements of occlusal force, predicted cognitive decline during the follow‐up period.

Conclusion

Several studies demonstrated a positive association between masticatory function and cognitive status. However, further studies, particularly longitudinal studies, are required to determine whether the association is causal.

DOI： 10.1111/ger.12751

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

PURPOSE: This prospective cohort study examined the effects of the number of present and functional teeth on mortality among older Japanese adults requiring nursing care in an environment of comprehensive oral hygiene and nutritional management. METHODS: The study included 174 older adults (mean age: 84.4 ± 8.3 years; male/female: 49/125) in need of support or long-term care, who resided in either a local specialized healthcare facility or their own homes, and received daily oral hygiene and nutritional support at facilities in Okayama, Japan. The initial clinical oral examination along with assessment of general physical condition and nursing environment of the participants were performed in July 2013 and followed up for one year. RESULTS: All-cause mortality occurred in 28 (mean age: 88.7 ±13.4 years; male/female: 6 /22) individuals during the follow-up period. Cox proportional hazard analysis indicated that older age, low performance in activities of daily living (Barthel Index <40), and underweight status (body mass index <18.5) were significant risk factors for mortality. The number of present and functional teeth were not found to be significant risk factors for mortality. CONCLUSIONS: During the one-year follow-up period, the number of present and functional teeth did not have a significant impact on mortality among older Japanese adults requiring nursing care in a well-managed environment of oral hygiene and nutritional status.

DOI： 10.2186/jpr.JPR_D_23_00221

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Mesenchymal stem cells (MSCs) are known to promote tissue regeneration and suppress excessive inflammation caused by infection or trauma. Reported evidence indicates that various factors influence the expression of MSCs' endogenous immunomodulatory properties. However, the detailed interactions of MSCs with macrophages, which are key cells involved in tissue repair, and their regulatory mechanisms are not completely understood. We herein investigated how age-related immunomodulatory impairment of MSCs alters the interaction of MSCs with macrophages during bone healing using young (5-week old) and aged (50-week old) mice. To clarify the relationship between inflammatory macrophages (M1) and MSCs, their spatiotemporal localization at the bone healing site was investigated by immunostaining, and possible regulatory mechanisms were analyzed in vitro co-cultures. Histomorphometric analysis revealed an accumulation of M1 and a decrease in MSC number at the healing site in aged mice, which showed a delayed bone healing. In in vitro co-cultures, MSCs induced M1 apoptosis through cell-to-cell contact but suppressed the gene expression of pro-inflammatory cytokines by soluble factors secreted in the culture supernatant. Interestingly, interleukin 38 (Il-38) expression was up-regulated in M1 after co-culture with MSCs. IL-38 suppressed the gene expression of inflammatory cytokines in M1 and promoted the expression of genes associated with M1 polarization to anti-inflammatory macrophages (M2). IL-38 also had an inhibitory effect on M1 apoptosis. These results suggest that MSCs may induce M1 apoptosis, suppress inflammatory cytokine production by M1, and induce their polarization toward M2. Nevertheless, in aged conditions, the decreased number and immunomodulatory function of MSCs could be associated with a delayed M1 clearance (i.e., apoptosis and/or polarization) and consequent delayed resolution of the inflammatory phase. Furthermore, M1-derived IL-38 may be associated with immunoregulation in the tissue regeneration site.

DOI： 10.3390/ijms25063252

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

OBJECTIVES: An increasing number of studies have identified an association between oral health status and cognitive function. However, the effect of oral interventions, including oral health care, dental treatment and oral motor exercises, on cognitive function remains unclear. This systematic review examined whether oral interventions contribute to the long-term improvement of cognitive status. METHODS: Four databases were searched (MEDLINE, Web of Science, Cochrane Library, and ICHUSHI Web) to identify randomized and nonrandomized controlled trial studies and prospective cohort studies from inception until 1 September 2023, published in English or Japanese. The Cochrane risk of bias tool for randomized controlled trials and the risk of bias assessment tool for nonrandomized studies were used to assess bias risk. RESULTS: A total of 20 articles were included in the qualitative analysis; 13 articles were published in English, and 7 were published in Japanese. The implemented interventions were oral care in 8 studies, dental treatment in 8 studies, and oral motor exercise in 4 studies. One study found a significant effect on attention following oral care intervention. Some dental treatments influenced cognitive function, although a clear positive effect was not determined. In 1 study, attention and working memory improved in the chewing exercise group. CONCLUSIONS: Several studies verified the improvement effects of oral interventions, such as oral care, dental treatment, and oral motor exercise, on cognitive function or impairment. However, there was still a lack of conclusive evidence that such an intervention clearly improved cognitive function. To clarify the effects of oral interventions on cognitive function, it is necessary to examine participants, interventions, and outcome measures in detail.

DOI： 10.1016/j.jebdp.2023.101948

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

PURPOSE: To compare the accuracy of the tooth morphology fusion (TMF) digital technique and customized impression transfer coping (conventional) technique when transferring the morphology of a provisional crown to a definitive screw-retained implant-supported crown. METHODS: Six cases of partial edentulism (one anterior and five posterior) treated with oral implant placement in our clinic for the loss of three or fewer teeth in the maxilla or mandible between April 2017 and September 2018 were included. After implant placement and re-entry surgery, provisional restorations were made and adjusted to obtain the ideal morphology. Two definitive restorations were constructed by transferring the complete morphology of the provisional restorations, including the subgingival contour, using the TMF digital and conventional techniques. Three sets of surface morphological data were obtained using a desktop scanner. The three-dimensional total discrepancy volume (TDV) between the provisional restoration (reference) and the two definitive restorations was digitally measured by overlapping the surface data of the stone cast using the Boolean operation. Each TDV ratio (%) was calculated by dividing the TDV by the volume of provisional restoration. The median TDV ratios for TMF and conventional techniques were compared using the Wilcoxon signed-rank test. RESULTS: The median TDV ratio between provisional and definitive restorations constructed using the TMF digital technique (8.05%) was significantly lower than that obtained using the conventional technique (13.56%, P < 0.05). CONCLUSIONS: In this preliminary intervention study, the TMF digital technique was more accurate than the conventional technique for the transfer of morphology from provisional to definitive prosthesis.

DOI： 10.2186/jpr.JPR_D_22_00244

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Authorship：Last author   Publishing type：Research paper (scientific journal)   Publisher：XMLink  

DOI： 10.4047/jap.2024.16.4.244

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Other Link： https://jap.or.kr/DOIx.php?id=10.4047/jap.2024.16.4.244

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

S-adenosylmethionine (SAM) is considered to be a useful therapeutic agent for degenerative cartilage diseases, although its mechanism is not clear. We previously found that polyamines stimulate the expression of differentiated phenotype of chondrocytes. We also found that the cellular communication network factor 2 (CCN2) played a huge role in the proliferation and differentiation of chondrocytes. Therefore, we hypothesized that polyamines and CCN2 could be involved in the chondroprotective action of SAM. In this study, we initially found that exogenous SAM enhanced proteoglycan production but not cell proliferation in human chondrocyte-like cell line-2/8 (HCS-2/8) cells. Moreover, SAM enhanced gene expression of cartilage-specific matrix (aggrecan and type II collagen), Sry-Box transcription factor 9 (SOX9), CCN2, and chondroitin sulfate biosynthetic enzymes. The blockade of the methionine adenosyltransferase 2A (MAT2A) enzyme catalyzing intracellular SAM biosynthesis restrained the effect of SAM on chondrocytes. The polyamine level in chondrocytes was higher in SAM-treated culture than control culture. Additionally, Alcian blue staining and RT-qPCR indicated that the effects of SAM on the production and gene expression of aggrecan were reduced by the inhibition of polyamine synthesis. These results suggest that the stimulation of polyamine synthesis and gene expression of chondrogenic differentiation factors, such as CCN2, account for the mechanism underlying the action of SAM on chondrocytes.

DOI： 10.3390/ijms242417294

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Language：Japanese   Publisher：(一社)日本口腔リハビリテーション学会  

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

PURPOSE: The aim of this study is to compare dental implant placement accuracy of three surgical guide fabrication methods: single (SCT) and double computed tomography (DCT), and a newly developed modified SCT (MSCT) scan method. METHODS: A total of 183 cases (183 surgical guides, and 485 implants) of static-guide-assisted implant placement surgery using the SCT, DCT, or MSCT methods in a dental clinic were included in the study. Three-dimensional (3D) deviations (mm) at the entry and tip of the implant body between preoperative simulation and actual placement were measured as surrogate endpoints of implant placement accuracy. The following survey details were collected from medical records and CT data: sex, age at implant placement surgery, surgical guide fabrication method, number of remaining teeth, implant length, implant location, alveolar bone quality, and bone surface inclination at implant placement site in preoperative simulation, etc. Risk factors for reducing implant placement accuracy were investigated using generalized estimating equations. RESULTS: The SCT and DCT methods (odds ratios [ORs] vs. MSCT method: 1.438, 1.178, respectively), posterior location (OR: 1.114), bone surface buccolingual inclination (OR: 0.997), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the entry; the SCT (OR: 1.361) and DCT methods (OR: 1.418), posterior location (OR: 1.190), implant length (OR: 1.051), and age at implant placement surgery (OR: 0.995) were significant risk factors for larger 3D deviation at the tip of the implant body. CONCLUSIONS: Implant placement accuracy was better using the MSCT method compared to the SCT and DCT methods.

DOI： 10.1186/s40729-023-00509-8

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Language：Japanese   Publisher：日本歯科衛生学会  

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

超高齢社会の本邦において認知症への対策は喫緊の課題であり,国の認知症施策推進総合戦略(新オレンジプラン)において歯科医師にも積極的な関与が求められている.歯学研究において,認知機能と口腔機能の関連は,関心が高いテーマで,これまでに基礎・臨床研究が多数報告されている.その一方,医科専門分野では口腔因子が認知機能の低下または認知症の発症のリスク因子として共有されるに至っていない.(公社)日本補綴歯科学会は,認知機能と口腔機能との相関について新たな研究を展開するために,(公社)日本老年精神医学会と連携して研究プロジェクトを推進している.本稿では,ECCOプロジェクトを設立した経緯と活動内容を概説する.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J05334&link_issn=&doc_id=20230127240010&doc_link_id=%2Fdv5proso%2F2023%2F001501%2F012%2F0072-0078%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdv5proso%2F2023%2F001501%2F012%2F0072-0078%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

DOI： 10.2186/ajps.15.72

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DOI： 10.2186/jpr.JPR_D_23_00251

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

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

AIM: To examine the relationship between the number of present and functional teeth at baseline and future incidence of loss of independence. METHODS: Participants were community-dwelling older individuals who participated in a comprehensive geriatric health examination conducted in Kusatsu town, Japan, between 2009 and 2015. The primary endpoint was the incidence of loss of independence among participants, defined as the first certification of long-term care insurance in Japan. The numbers of present and functional teeth at baseline were determined via an oral examination. Demographics, clinical variables (e.g., history of chronic diseases and psychosocial factors), blood nutritional markers, physical functions, and perceived masticatory function were assessed. RESULTS: This study included 1121 individuals, and 205 individuals suffered from loss of independence during the follow-up period. Kaplan-Meier estimates of loss of independence for participants with smaller numbers of present and functional teeth were significantly greater than for those with larger numbers of teeth. Cox proportional hazard analyses indicated that a smaller number of present teeth was not a significant risk factor after adjusting for demographic characteristics. However, the number of functional teeth was a significant risk factor after the adjustment (hazard ratio: 1.975 [1.168-3.340]). Additionally, higher hazard ratios were observed in other adjusted models, but they were not statistically significant. CONCLUSIONS: The number of functional teeth may be more closely related to the future incidence of loss of independence than the number of present teeth. This novel finding suggests that prosthodontic rehabilitation for tooth loss possibly prevents the future incidence of this life-event. Geriatr Gerontol Int 2022; ••: ••-••.

DOI： 10.1111/ggi.14508

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Language：Japanese   Publisher：日本口腔リハビリテーション学会  

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Language：Japanese   Publisher：(一社)日本口腔リハビリテーション学会  

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Language：Japanese   Publisher：岡山歯学会  

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

In our search for innovative drugs that could improve periodontal treatment outcomes, autophagy and its anomalies represent a potential target for therapeutic intervention. We sought to identify autophagy defects in murine experimental periodontitis and study the effectiveness of P140, a phosphopeptide known to bind HSPA8 and inhibit its chaperone properties, and that corrects autophagy dysfunctions in several autoimmune and inflammatory diseases. Experimental periodontitis was induced by placing silk ligature around mandibular first molars. Sick mice were treated intraperitoneally with either P140 or a control, scrambled peptide. After 10 days, mandibles were harvested and bone loss was measured by micro-CT. Immune cells infiltration was studied by histological analyses. Cytokines levels and autophagy-related markers expression were evaluated by qRT-PCR and western blotting. A comparison with non-affected mice revealed significant alterations in the autophagy processes in mandibles of diseased mice, especially in the expression of sequestosome 1/p62, Maplc3b, Atg5, Ulk1, and Lamp2. In vivo, we showed that P140 normalized the dysregulated expression of several autophagy-related genes. In addition, it diminished the infiltration of activated lymphocytes and pro-inflammatory cytokines. Unexpectedly P140 decreased the extent of bone loss affecting the furcation and alveolar areas. Our results indicate that P140, which was safe in clinical trials including hundreds of autoimmune patients with systemic lupus erythematosus, not only decreases the inflammatory effects observed in mandibular tissues of ligation-induced mice but strikingly also contributes to bone preservation. Therefore, the therapeutic peptide P140 could be repositioned as a decisive breakthrough for the future therapeutic management of periodontitis.

DOI： 10.1007/s00018-022-04537-2

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

PURPOSE: The aim of this study was to introduce rating criteria to evaluate student performance in a newly developed, digital wax-up preclinical program for computer-aided design (CAD) of full-coverage crowns and preliminarily investigate the reliability and internal consistency of the rating system. MATERIALS AND METHODS: This study, conducted in 2017, enrolled 47 fifth-year dental students of Okayama University Dental School. Digital wax-up training included a fundamental practice using computer graphics (CG), multipurpose CAD software programs, and an advanced practice to execute a digital wax-up of the right mandibular second molar (#47). Each student's digital wax-up work (stereolithography data) was evaluated by two instructors using seven qualitative criteria. The total qualitative score (0-90) of the criteria was calculated. The total volumetric discrepancy between each student's digital wax-up work and a reference prepared by an instructor was automatically measured by the CAD software. The inter-rater reliability of each criterion was analyzed using a weighted kappa index. The relationship between the total volume discrepancy and the total qualitative score was analyzed using Spearman's correlation. RESULTS: The weighted kappa values for the seven qualitative criteria ranged from 0.62 - 0.93. The total qualitative score and the total volumetric discrepancy were negatively correlated (ρ = -0.27, P = .09, respectively); however, this was not statistically significant. CONCLUSION: The established qualitative criteria to evaluate students' work showed sufficiently high inter-rater reliability; however, the digitally measured volumetric discrepancy could not sufficiently predict the total qualitative score.

DOI： 10.4047/jap.2022.14.4.203

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Purpose To investigate the effect of prosthodontic treatment on the ingestible food profile in adult Japanese outpatients, and to identify the related risk factors that can deteriorate the profile.Methods The participants were 277 outpatients who visited university-based specialty clinics in Japan for prosthodontic treatment. The demographic data, number of present teeth assessed via intraoral examination, and oral health-related quality of life assessed by the total Oral Health Impact Profile (OHIP-J54) scores of all participants were recorded before treatment. Ingestible food profile score (IFS) was recorded using a validated food intake questionnaire. Eligible participants who answered the questionnaire before and after treatment were categorized into five groups based on the prosthodontic treatments they received (i.e., crowns, bridges, removable partial dentures, removable complete dentures, and removable complete and partial dentures).Results Multivariate analysis of covariance revealed a statistically significant main effect of prosthodontic intervention (time course: before and after treatment) on mean IFS (p=0.035, F=4.526), even after adjusting for covariates (age, number of present teeth, and treatment modality). Multiple linear regression analysis revealed that the low number of present teeth (r=0.427, p<0.001) and a high OHIP-J54 total score (r=-0.519, p<0.001) of the patients at the baseline were significantly associated with their baseline IFSs, even after adjusting for confounding variables.Conclusions The findings of this multicenter follow-up study indicate the importance of prosthodontic rehabilitation in improving patients' ingestible food profiles.

DOI： 10.2186/jpr.JPR_D_22_00017

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

We introduce a new digital workflow to fabricate a fixed partial denture (FPD) utilizing the three-dimensional surface morphology of provisional restoration (PR) and abutment teeth. Scanned images of the full maxilla with abutment teeth, full maxilla with PR, and PR alone were superimposed. The surfaces of the final FPD were designed based on the entire morphology of the PR and abutment teeth surfaces. The inner and outer surfaces converged at the margin lines of the abutment teeth. Fine modifications to the final FPD design were performed manually, and the final FPD was fabricated and successfully installed in the patient.

DOI： 10.18926/AMO/63215

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PATIENT: A 54-year-old woman presenting with anterior alveolar ridge resorption was submitted to a connective tissue graft (CTG) for esthetic improvement before rehabilitation with a fixed partial denture. Palate-harvested connective tissue was used as a graft after extra-oral removal of the epithelium. Unexpectedly, complete wound healing was not observed. Moreover, 6 months post-surgery, a white discharge was detected at the grafted site. The adjacent tooth showing a root fracture was initially associated with the symptoms and was then extracted. Concomitantly, the unhealed tissue at the grafted site was also excised, leading to temporary symptom resolution. However, the white discharge reappeared after 2 months. The excision area was expanded to remove the grafted tissue entirely, and the wound was completely healed. Since the alveolar ridge resorption had become larger compared to the preoperative condition, the patient was subjected to a second CTG, now using a connective tissue harvested from the palate by a single incision technique. The wound healed uneventfully, and the final prosthesis was delivered 6 months after soft tissu e stabilization. The patient has been followed-up for more than 28 months without any recurrence of white discharge. DISCUSSION: Histopathological and cytological examination detected keratinized epithelial tissues and cells, respectively, in excised tissues and white discharge specimens. Consequently, a possible relationship between white discharge and residual epithelium in the harvested graft was strongly suspected. CONCLUSIONS: Success of the CTG procedure requires careful method selection for tissue transplantation and treatment execution.

DOI： 10.2186/jpr.JPR_D_20_00115

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PURPOSE: Dental implant therapy is a common clinical treatment for missing teeth. However, the esthetic result is not as satisfactory as expected in some cases, especially in the anterior maxillary area. Poor esthetic results are caused by inadequate preparation of the hard and soft tissues in this area before treatment. The socket shield technique may be an alternative for a desirable esthetic outcome in dental implant treatments. STUDY SELECTION: In the present systematic review, PubMed-Medline, Google Scholar, and ScienceDirect were searched for clinical studies published from January 2000 to December 2018. RESULTS: Twenty studies were included, comprising one randomized controlled trial, two cohort studies, 14 clinical human case reports, and three retrospective case series. In total, 288 patients treated with the socket shield technique with immediate implant placement and follow-up between 3-60 months after placement were included. A quality assessment showed that 12 of the 20 included studies were of good quality. Twenty-six of the 274 (9.5%) cases developed complications or adverse effects related to the socket shield technique. Most studies reported implant survival without the complications (90.5%); most of the cases that were followed up for more than 12 months after implant placement achieved a good esthetic appearance. The failure rate was low without the complications, although there were some failures due to failed implant osseointegration, socket shield mobility and infection, socket shield exposure, socket shield migration, and apical root resorption. CONCLUSIONS: The socket shield technique can be used in dental implant treatment, but it remains difficult to predict the long-term success of this technique until high-quality evidence becomes available.

DOI： 10.2186/jpr.JPR_D_20_00054

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PURPOSE: Bone morphogenetic protein (BMP)-2 is a potent growth factor that is widely used in the orthopedic and dental fields for bone regeneration.However, recombinant human BMP-2 (rhBMP-2) products have not been legally approved in Japan. Recently, our research group succeeded in producing GMP-grade rhBMP-2 using the E. coli system (E-rhBMP-2) at the industrial level and developed E-rhBMP-2 adsorbed onto β-TCP (E-rhBMP-2/β-TCP) as an alternative material to autogenous bone grafts. Previous studies on the toxicity, pharmacokinetics, and optimal doses of E-rhBMP-2 have confirmed its safety and efficiency. However, comparative studies with standard treatment therapies are still necessary before clinical application in humans. Therefore, in this preclinical study, we compared the bone regeneration ability of E-rhBMP-2/β-TCP and autogenous bone grafts in a canine guided-bone regeneration model. METHODS: Following extraction of the maxillary third premolar, box-type bone defects (10 mmL × 4 mmW × 9 mmH) were created in the extraction socket area and transplanted with E-rhBMP-2/β-TCP or autogenous bone graft in a canine. After 8 weeks, micro-CT and histological analyses were performed. RESULTS: Transplantation of both E-rhBMP-2/β-TCP and autogenous bone graft significantly promoted bone formation compared to the non-transplantation control group. The bone formation ability of E-rhBMP-2/β-TCP was equal to that of the autogenous bone graft. Histological analysis showed that excessive infiltration of inflammatory cells and residual β-TCP particles mostly were not observed in the E-rhBMP-2/β-TCP transplantation group. CONCLUSIONS: This preclinical study demonstrated that E-rhBMP-2/β-TCP and autogenous bone have equal potential to promote bone regeneration.

DOI： 10.2186/jpr.JPR_D_20_00226

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OBJECTIVES: In this study, we aimed to compare the long-term survival of vital teeth adjacent to bounded edentulous spaces rehabilitated using an implant-supported prosthesis (ISP), a resin-bonded fixed partial denture (RBFPD), or a conventional fixed partial denture (CFPD). The risk factors for complications in teeth adjacent to the edentulous space (TAES) were also investigated. METHODS: We followed-up a consecutive series of 514 patients who underwent rehabilitation of a single bounded edentulous space with vital TAES (ISP: 103; RBFPD: 216; and CFPD: 195) from 2008 to 2017. Cumulative survival rates of prosthesis and TAES, and complication-free rates of TAES, were evaluated using the Kaplan-Meier analysis and log-rank test. Risk factors were evaluated using a Cox proportional hazards model. RESULTS: Cumulative complication-free rates of TAES showed no significant differences among the three groups. The cumulative survival rate of TAES in CFPD was significantly lower than that of ISP (p = 0.037); no significant differences were observed between ISP and RBFPD (p = 0.513), and RBFPD and CFPD (p = 0.076). Older age (p = 0.027) was the only independent significant risk factor for complications in TAES. Installation of CFPD (p = 0.019), ceramic prosthesis in edentulous space (p = 0.026), and deeper periodontal probing depth (p = 0.018) of TAES were significant risk factors for non-surviving TAES. CONCLUSIONS: Rehabilitating a single bounded edentulous space with CFPD could increase the risk for TAES loss compared with ISP. Risk of TAES loss remained similar between ISP and RBFPD, which can minimize the loss of coronal tooth structure during tooth preparation. CLINICAL SIGNIFICANCE: Teeth adjacent to edentulous space show equivalent longevity when rehabilitating a single bounded edentulous space with resin-bonded fixed partial dentures or single standing implant-supported prosthesis, at least 10 years post-installation.

DOI： 10.1016/j.jdent.2021.103911

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

DOI： 10.2186/jpr.jpr_d_20_00272

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Medication-related osteonecrosis of the jaw (MRONJ) is related to impaired bone healing conditions in the maxillomandibular bone region as a complication of bisphosphonate intake. Although there are several hypotheses for the onset of MRONJ symptoms, one of the possible causes is the inhibition of bone turnover and blood supply leading to bone necrosis. The optimal treatment strategy for MRONJ has not been established either. BMP-2, a member of the TGF-β superfamily, is well known for regulating bone remodeling and homeostasis prenatally and postnatally. Therefore, the objectives of this study were to evaluate whether cyclophosphamide/zoledronate (CY/ZA) induces necrosis of the bone surrounding the tooth extraction socket, and to examine the therapeutic potential of BMP-2 in combination with the hard osteoinductive biomaterial, β-tricalcium phosphate (β-TCP), in the prevention and treatment of alveolar bone loss around the tooth extraction socket in MRONJ-like mice models. First, CY/ZA was intraperitoneally administered for three weeks, and alveolar bone necrosis was evaluated before and after tooth extraction. Next, the effect of BMP-2/β-TCP was investigated in both MRONJ-like prevention and treatment models. In the prevention model, CY/ZA was continuously administered for four weeks after BMP-2/β-TCP transplantation. In the treatment model, CY/ZA administration was suspended after transplantation of BMP-2/β-TCP. The results showed that CY/ZA induced a significant decrease in the number of empty lacunae, a sign of bone necrosis, in the alveolar bone around the tooth extraction socket after tooth extraction. Histological analysis showed a significant decrease in the necrotic alveolar bone around tooth extraction sockets in the BMP-2/β-TCP transplantation group compared to the non-transplanted control group in both MRONJ-like prevention and treatment models. However, bone mineral density, determined by micro-CT analysis, was significantly higher in the BMP-2/β-TCP transplanted group than in the control group in the prevention model only. These results clarified that alveolar bone necrosis around tooth extraction sockets can be induced after surgical intervention under CY/ZA administration. In addition, transplantation of BMP-2/β-TCP reduced the necrotic alveolar bone around the tooth extraction socket. Therefore, a combination of BMP-2/β-TCP could be an alternative approach for both prevention and treatment of MRONJ-like symptoms.

DOI： 10.3390/ijms222312823

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN PROSTHODONTIC SOC  

PURPOSE: The purpose of the study was to compare the long-term performance of three prostheses for partial edentulism: implant-supported, fixed denture (IFD), fixed partial denture (FPD), and removable partial denture (RPD), in terms of prosthesis survival and oral health-related quality of life (OHRQoL). METHODS: The 138 patients in our previous study (Kimura et al., 2012) received one of the three prosthetic treatments and answered a validated OHRQoL questionnaire before and immediately after treatment. In the present study, the patients were followed up six years after treatment using medical records and OHRQoL examinations to evaluate prosthesis survival and change in OHRQoL. The cumulative survival rates were calculated using the Kaplan-Meier analysis. The Steel-Dwass test was used to compare the median OHRQoL scores at the three time points. RESULTS: For the 105 patients (66.8 ± 10.8 years, IFD/FPD/RPD: 58/27/20 patients) who successfully completed the follow-up assessments, the six-year estimated cumulative survival rates of the IFDs, FPDs, and RPDs were 94.7%, 77.4%, and 33.3%, respectively. The log-rank tests indicated that the survival curves were significantly different (IFDs vs. FPDs: p = 0.01; RPDs vs. IFDs, FPDs: p < 0.01). The median OHRQoL scores of the IFD group immediately after treatment and six years after treatment were significantly higher than those observed before treatment (p < 0.01). There was no significant difference in the median OHRQoL scores among the three time points in the RPD or FPD groups. CONCLUSIONS: IFDs showed significantly longer survival rates than FPDs and RPDs in partially edentulous patients. Only in the IFD patients was the OHRQoL level six years after treatment significantly higher than that b efore treatment.

DOI： 10.2186/jpr.JPR_D_20_00095

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Language：Japanese   Publisher：(株)ヒョーロン・パブリッシャーズ  

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Language：Japanese  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J02151&link_issn=&doc_id=20210909260002&doc_link_id=10.11237%2Fjsoi.34.115&url=https%3A%2F%2Fdoi.org%2F10.11237%2Fjsoi.34.115&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(株)ヒョーロン・パブリッシャーズ  

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Language：Japanese   Publisher：(一社)日本口腔顔面痛学会  

目的:高齢者人口の増加に伴う認知症の有病率上昇は、介護、医療の負担を増大させる深刻な社会問題となっている。本疾患による自立低下は、口腔内のセルフケア能力の低下などを介して健全な口腔、咀嚼機能の維持を困難とし、口腔顔面痛疾患罹患のリスクを高めることが予測される。しかしながら両者の関係については不明な点が多い。本総説の目的は、現時点での認知機能低下、認知症と口腔顔面痛の関係に関する知見をまとめ、今後の問題点と展望を考えることである。研究の選択:認知機能低下、認知症と口腔顔面痛をキーワードに、PubMedと医中誌から文献検索を行った。定めた検索式で抽出した原著論文の文献数は少なく、検索から採用した文献の引用文献と、ハンドサーチで得られた文献をもとに文献レビューを行った。結果:認知機能低下、認知症高齢者においては口腔顔面痛の有症状率が高いという報告と、低いことを示す結果を得た報告が存在した。口頭で痛みを訴えることができない状態では、正確な診断につながらず、実際の有症状率より低く検出されている可能性も考えられた。また、口頭で症状を訴えることが不可能なこれらの患者に対する現在の口腔顔面痛の診査、診断方法は、未だ不十分であることが明らかとなった。結論:未曾有の超高齢社会を迎えた現在、認知機能の低下した高齢者に対する適切な口腔顔面痛の診査、診断方法の確立は急務と考えられた。(著者抄録)

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Language：Japanese   Publisher：日本口腔顎顔面技工学会  

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

われわれ歯科医は補綴治療を毎日患者に施しているが,その治療がどのような効果を患者に及ぼしているかを十分認識していない.たとえば,自立した地域在住高齢者においては,補綴治療の主目的は,口腔関連QOLの向上に加えて,介護予防,フレイル予防,認知機能低下予防であり,補綴治療による口腔機能の維持は多様な食物や栄養素を摂取するという観点から重要な意味があると言われている.本論説では,近年発表された質の高いシステマティックレビューと原著論文を精読し,地域在住高齢者においては,現在歯数が多いほど,生命予後が良好であること,また,現在歯数よりも機能歯数の方が生命予後に強く関連するという日本補綴歯科学会と東京都健康長寿医療センターの共同研究結果を紹介した.一方,日常生活動作がまだまだ保たれている前期要支援・要介護高齢者においては,歯列欠損の修復に加えて,栄養摂取強化と広義の摂食嚥下リハビリテーションが重要な意味を持つ.また,日常生活動作が著しく低下する後期要介護高齢者においては,食環境や食形態の調整,栄養補助食品の利用,多様な栄養摂取ルートの活用などが必要になる.これらの臨床エビデンスをライフステージに合わせて読み解くことにより,われわれ補綴歯科医の医学的,社会的な責務が,どのライフステージにおいても甚大であることを訴えたい.(著者抄録)

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PATIENTS: The patient was a 55-year-old woman with left upper molar free-end edentulism and 9 full cast metal crowns in her mouth. Three three-dimensional (3D) images were superimposed: a computed tomography (CT) image with the patient wearing the CT-matching template (CTMT) with six glass ceramic markers, which hardly generate any artifacts, on the template surface, and oral plaster model surfaces with and without CTMTs. Metal artifacts were automatically removed by a Boolean operation identifying unrealistic images outside the oral plaster model surface. After the preoperative simulation, fully guided oral implant surgery was performed. Two implant bodies were placed in the left upper edentulism. The placement errors calculated by comparing the preoperative simulation and actual implant placement were then assessed by a software program using the 3D-CT bone morphology as a reference. The 3D deviations between the preoperative simulation and actual placement at the entry of the implant body were a maximum 0.48 mm and minimum 0.26 mm. Those at the tip of the implant body were a maximum 0.56 mm and a minimum 0.25 mm. DISCUSSION: In this case, the maximum 3D deviations at the entry and tip section were less than in previous studies using double CT. CONCLUSIONS: Accurate image fusion utilizing CTMT with new reference markers was possible for a patient with many metal restorations. Using a surgical guide manufactured by the new matching methodology (modified single CT scan method), implant placement deviation can be minimized in patients with many metal restorations.

DOI： 10.2186/jpr.JPOR_2019_429

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

Aging tissues present a progressive decline in homeostasis and regenerative capacities, which has been associated with degenerative changes in tissue-specific stem cells and stem cell niches. We hypothesized that amino acids could regulate the stem cell phenotype and differentiation ability of human bone marrow-derived mesenchymal stromal cells (hBMSCs). Thus, we performed a screening of 22 standard amino acids and found that D-tryptophan (10 μM) increased the number of cells positive for the early stem cell marker SSEA-4, and the gene expression levels of OCT-4, NANOG, and SOX-2 in hBMSCs. Comparison between D- and L-tryptophan isomers showed that the latter presents a stronger effect in inducing the mRNA levels of Oct-4 and Nanog, and in increasing the osteogenic differentiation of hBMSCs. On the other hand, L-tryptophan suppressed adipogenesis. The migration and colony-forming ability of hBMSCs were also enhanced by L-tryptophan treatment. In vivo experiments delivering L-tryptophan (50 mg/kg/day) by intraperitoneal injections for three weeks confirmed that L-tryptophan significantly increased the percentage of cells positive for SSEA-4, mRNA levels of Nanog and Oct-4, and the migration and colony-forming ability of mouse BMSCs. L-kynurenine, a major metabolite of L-tryptophan, also induced similar effects of L-tryptophan in enhancing stemness and osteogenic differentiation of BMSCs in vitro and in vivo, possibly indicating the involvement of the kynurenine pathway as the downstream signaling of L-tryptophan. Finally, since BMSCs migrate to the wound healing site to promote bone healing, surgical defects of 1 mm in diameter were created in mouse femur to evaluate bone formation after two weeks of L-tryptophan or L-kynurenine injection. Both L-tryptophan and L-kynurenine accelerated bone healing compared to the PBS-injected control group. In summary, L-tryptophan enhanced the stemness and osteoblastic differentiation of BMSCs and may be used as an essential factor to maintain the stem cell properties and accelerate bone healing and/or prevent bone loss.

DOI： 10.3390/ma14010208

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

Background/purpose: Color-changeable chewing gum is used for the evaluation of masticatory performance. However, it is currently unclear whether colorimetric and visual assessment methods yield consistent results. This study aimed to clarify the consistency between colorimetric and visual methods used for the evaluation of color changes in color-changeable chewing gum. Materials and methods: The sample comprised 644 older persons (mean age, 75.4 ± 6.4 years). The chewing gum was masticated 60 times at the participant's own chewing rate and then expectorated. The color of the chewing gum was evaluated with the ΔE values and a∗ values, measured using a colorimeter, and the 10 Color Shades (10CSh) and 5 Color Scales (5CSc), using visual evaluation. Spearman's correlation analysis was performed to examine the correlation between the results obtained by the four methods. The significance level was set at α = 0.05. Results: The ΔE values, a∗ values, 10CSh scores, and 5CSc scores were all significantly correlated. The highest correlation coefficient (0.979) was between the ΔE values and a∗ values. The lowest correlation coefficient (0.847) was between the a∗ values and 5CSc scores. Decreased masticatory performance was observed with increased age. Conclusion: Significant correlations were found for all four methods used in the assessment of masticatory performance with color-changeable chewing gum. While visually based assessments are valid, colorimetric methods are more sensitive to smaller changes in masticatory performance.

DOI： 10.1016/j.jds.2020.08.010

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Publishing type：Research paper (scientific journal)   Publisher：Japan Prosthodontic Society  

DOI： 10.2186/ajps.13.117

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Language：Japanese   Publisher：(株)ヒョーロン・パブリッシャーズ  

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Mesenchymal stem cells (MSCs) are known to play important roles in the repair of lost or damaged tissues and immunotolerance. On the other hand, aging is known to impair MSC function. However, little is currently known about how aged MSCs affect the host response to the local inflammatory condition and tissue deterioration in periodontitis, which is a progressive destructive disease of the periodontal tissue potentially leading to multiple tooth loss. In this study, we examined the relationship between aging-induced impairment of MSC function and the severity of periodontal tissue destruction associated with the decrease in host immunomodulatory response using a ligature-induced periodontitis model in young and aged mice. The results of micro computerized tomography (micro-CT) and histological analysis revealed a more severe bone loss associated with increased osteoclast activity in aged (50-week-old) mice compared to young (5-week-old) mice. Immunostaining analysis revealed that, in aged mice, the accumulation of inflammatory T and B cells was higher, whereas the percentage of platelet-derived growth factor receptor α (PDGFRα)+ MSCs, which are known to modulate the apoptosis of T cells, was significantly lower than in young mice. In vitro analysis of MSC function showed that the expression of surface antigen markers for MSCs (Sca-1, CD90, CD146), colony formation, migration, and osteogenic differentiation of aged MSCs were significantly declined compared to those of young MSCs. Moreover, a significantly higher proportion of aged MSCs were positive for the senescence-associated β galactosidase activity. Importantly, aged MSCs presented a decreased expression of FAS-L, which was associated with a lower immunomodulatory property of aged MSCs to induce T cell apoptosis in co-cultures compared with young MSCs. In summary, this is the first study showing that aging-induced impairment of MSC function, including immunomodulatory response, is potentially correlated with progressive periodontal tissue deterioration.

DOI： 10.3390/ijms21218103

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Bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2) have been regarded as the major cytokines promoting bone formation, however, several studies have reported unexpected results with failure of bone formation or bone resorption of these growth factors. In this study, BMP-2 and FGF-2 adsorbed into atellocollagen sponges were transplanted into bone defects in the bone marrow-scarce calvaria (extramedullary environment) and bone marrow-abundant femur (medullary environment) for analysis of their in vivo effects not only on osteoblasts, osteoclasts but also on bone marrow cells. The results showed that BMP-2 induced high bone formation in the bone marrow-scarce calvaria, but induced bone resorption in the bone marrow-abundant femurs. On the other hand, FGF-2 showed opposite effects compared to those of BMP-2. Analysis of cellular dynamics revealed numerous osteoblasts and osteoclasts present in the newly-formed bone induced by BMP-2 in calvaria, but none were seen in either control or FGF-2-transplanted groups. On the other hand, in the femur, numerous osteoclasts were observed in the vicinity of the BMP-2 pellet, while a great number of osteoblasts were seen near the FGF-2 pellets or in the control group. Of note, FCM analysis showed that both BMP-2 and FGF-2 administrated in the femur did not significantly affect the hematopoietic cell population, indicating a relatively safe application of the two growth factors. Together, these results indicate that BMP-2 could be suitable for application in extramedullary bone regeneration, whereas FGF-2 could be suitable for application in medullary bone regeneration.

DOI： 10.3390/ijms21217967

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Language：Japanese   Publisher：日本保健医療福祉連携教育学会  

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Medication-related osteonecrosis of the jaw (MRONJ) is a severe pathological condition associated mainly with the long-term administration of bone resorption inhibitors, which are known to induce suppression of osteoclast activity and bone remodeling. Bone Morphogenetic Protein (BMP)-2 is known to be a strong inducer of bone remodeling, by directly regulating osteoblast differentiation and osteoclast activity. This study aimed to evaluate the effects of BMP-2 adsorbed onto beta-tricalcium phosphate (β-TCP), which is an osteoinductive bioceramic material and allows space retention, on the prevention and treatment of MRONJ in mice. Tooth extraction was performed after 3 weeks of zoledronate (ZA) and cyclophosphamide (CY) administration. For prevention studies, BMP-2/β-TCP was transplanted immediately after tooth extraction, and the mice were administered ZA and CY for an additional 4 weeks. The results showed that while the tooth extraction socket was mainly filled with a sparse tissue in the control group, bone formation was observed at the apex of the tooth extraction socket and was filled with a dense connective tissue rich in cellular components in the BMP-2/β-TCP transplanted group. For treatment studies, BMP-2/β-TCP was transplanted 2 weeks after tooth extraction, and bone formation was followed up for the subsequent 4 weeks under ZA and CY suspension. The results showed that although the tooth extraction socket was mainly filled with soft tissue in the control group, transplantation of BMP-2/β-TCP could significantly accelerate bone formation, as shown by immunohistochemical analysis for osteopontin, and reduce the bone necrosis in tooth extraction sockets. These data suggest that the combination of BMP-2/β-TCP could become a suitable therapy for the management of MRONJ.

DOI： 10.3390/ijms21197028

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Language：Japanese   Publisher：クインテッセンス出版(株)  

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AIM: Previous studies on the association between intraoral conditions and mortality in community-dwelling older individuals reported that fewer present teeth (PT) are significant risk factors for mortality. However, how the number of PT relative to the number of functional teeth (FT), including both present and rehabilitated teeth, influences mortality has not been investigated fully. This study examined the impact of the number of FT on mortality among community-dwelling Japanese older adults. METHODS: This study was a retrospective, observational and population-based follow-up study, which examined 1188 older individuals who participated in an annual geriatric health examination from 2009 to 2015. The average follow-up period was 1697.0 ± 774.5 days. The primary outcome was all-cause mortality at follow-up. The numbers of PT and FT of each participant were counted during an oral examination. In addition, demographics, clinical variables, blood nutrient markers, physical functions and perceived masticatory function were measured. RESULTS: Kaplan-Meier analysis, followed by a log-rank test, revealed that fewer PT (P < 0.001) and FT (P = 0.002) were significantly associated with a reduced survival rate. Cox's proportional hazard analysis indicated that the number of FT, but not the number of PT, was a significant independent mortality risk factor after adjusting for demographics, clinical variables, nutrient markers and physical functioning (P = 0.036, hazard ratio: 2.089). CONCLUSIONS: Current results suggest that the number of FT more strongly predicts all-cause mortality than the number of PT among community-dwelling older adults. Further studies are necessary to consider the confounding of socioeconomic status and disability status. Geriatr Gerontol Int 2020; ••: ••-••.

DOI： 10.1111/ggi.13911

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

OBJECTIVE: This study aims to verify the associations among sleep bruxism (SB), sleep arousal (SA) and concurrent body movements. MATERIAL AND METHODS: Subjects underwent a standard overnight polysomnography test and audio-video recordings. Sleep quality was evaluated according to the Rechtschaffen and Kales criteria, while SA was determined as per the American Sleep Disorders Association criteria. Analyses were performed by an external institution after masking of the subjects' information. SB was assessed based on the presence/absence of rhythmic masticatory muscle activity (RMMA) episodes, which were identified by using electromyography of the masseter muscle. The observed simultaneous movements included lower leg movement (LLM), swallowing, face scratching, head movement, body movement, eye blinking, coughing, licking, sighing, body scratching, lip sucking, somniloquy and yawning. The LLM was determined visually, as well as through an increase in the tibialis electromyogram signal. Other movements were visually assessed using audio-video recordings. The incidences of all the simultaneous movements were compared between RMMA with intercurrent SA (SAwRMMA; RMMA episode derived from a masseter electromyogram showing more than 10% of maximum voluntary contraction) and SA without RMMA (SAw/oRMMA). RESULTS: Fourteen subjects were included in this study (females/males: 4/10, mean age: 31.5 ± 5.7 years). Among these, LLM, swallowing, body movement, licking, body scratching and lip sucking were frequently observed in SAwRMMA episodes than in SAw/oRMMA episodes, significantly. However, the non-specific simultaneous movements were higher observed in SAw/oRMMA episodes than that in SAwRMMA. CONCLUSION: Our results suggest that SB is concurrently activated with LLM in relation to arousal.

DOI： 10.1111/joor.12913

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Informa {UK} Limited  

OBJECTIVE: To estimate the effect of a vibratory splint (VibS) in reducing sleep clenching (SC) and TMD pain. METHODS: Target sample was consecutive 19 TMD patients attending the Orofacial Pain Clinic at FFO-FOUSP. Patients used the VibS or acrylic occlusal splint (OS) as control for 14 days. Outcome variables were SC frequency and pain, assessed by a portable electromyography detector-analyzer (BiteStrip™) and 100 mm VAS, respectively. Statistical analyses were performed with two-way repeated measures ANOVA, and analysis of covariance (ANCOVA). RESULTS: VibS promoted a marked decrease, whereas acrylic OS increased SC frequency after two weeks of use. Due to a significant difference in initial VAS levels between VibS and control group, the effect of the two splints on TMD pain could not be clearly estimated. CONCLUSION: The results suggested that VibS can potentially be used to reduce SC frequency, although further studies with larger sample size are necessary to confirm these findings.

DOI： 10.1080/08869634.2018.1488652

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ALLEN PRESS INC  

DOI： 10.1563/aaid-joi-D-19-00064

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Language：English   Publisher：WILEY  

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AIM: The importance of oral care has been recognized for the prevention of airway infections in older individuals who require long-term care. The present prospective cohort study was carried out a decade ago to identify risk factors with numerous intraoral conditions as possible predictors involved in the onset of pneumonia and acute viral respiratory infection (AVRI) in older people requiring long-term care during a 6-month follow-up period (including winter). METHODS: This study included 1785 older individuals residing in 31 long-term care facilities in which dental hygienists were involved in instruction on daily oral care. Primary end-points were development of pneumonia and AVRI during the 6-month follow-up period. Several factors related to each participant's general condition, oral environment, swallowing function and vaccinations (or lack thereof) were evaluated by calibrated dentists and dental hygienists before the study onset. RESULTS: During the 6-month follow-up period, 74 participants (4.1%) developed pneumonia, and 28 participants (1.6%) developed AVRI. Cox proportional hazard analysis showed that poor nutritional status and the presence of dysphagia were significant risk factors for pneumonia onset. The presence of dry mouth and halitosis were significant risk factors for AVRI. CONCLUSIONS: This prospective multicenter cohort study identified poor nutritional status and dysphagia as independent risk factors for the development of pneumonia, and dry mouth and halitosis as independent risk factors for the development of AVRI in older people who require long-term care and who routinely receive professional oral care. Geriatr Gerontol Int 2019; 19: 1136-1140.

DOI： 10.1111/ggi.13784

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

目的:日本補綴歯科学会は、補綴歯科治療を必要とする患者の複雑な多様性を評価し、それをもとに難易度分類を行うことを目的に「補綴歯科治療の難易度を測定する多軸診断プロトコル」を作成し、すでに臨床上十分な信頼性を示すことを確認した。本研究では多施設臨床追跡研究により本プロトコルの妥当性を検討した。方法:新たに作成した多軸診断プロトコルは、口腔内の状態、身体社会的状態、口腔関連QOL(OHIP-J54)、精神心理学的状態の4つの診断軸からなる。それぞれグレード0(易しい)から3(難しい)の4段階評価を行う。日本補綴歯科学会の認定研修施設である大学病院補綴科9施設で、歯質もしくは歯列欠損に対し補綴歯科治療が必要と判断された初診患者を連続サンプリングした。補綴歯科治療前に、本プロトコルを用いて難易度評価を行った。そして補綴歯科治療後に、治療に要した時間、医療費などの医療資源および口腔関連QOL評価を行った。本プロトコルの構成概念妥当性は、治療前の術者の主観による難易度評価と、本プロトコルの各軸の難易度の相関を求め検討した。予測妥当性は、総医療費、総治療時間、治療前後の口腔関連QOL変化量をサロゲートエンドポイントとして用い、本プロトコルの4つの診断軸の難易度を統合した総合難易度との相関を求めた。結果と考察:口腔内の状態(Axis I)、身体社会的状態(Axis II)、口腔関連QOL(Axis III)と治療前の術者の主観による難易度評価は、有意な正の相関を示した。一方、精神心理学的状態(Axis IV)と治療前の術者の主観による難易度評価には相関が認められなかった。術前に本プロトコルで評価した患者の総合難易度は、治療の難易度とよく関連すると考えられるサロゲートエンドポイント(総治療費、総治療時間、口腔関連QOL改善量)のいずれとも有意に相関した。口腔内状況別にこの関係を精査すると、術前の総合難易度評価は、全部歯列欠損症例や部分歯列欠損症例においては、これらのサロゲートエンドポイントの一部と有意に相関が認められたが、全部歯列欠損と部分歯列欠損の混合症例や歯の問題の症例においては、それらのサンプルサイズが小さいこともあり有意差が認められなかった。結論:補綴歯科治療の難易度を初めて多軸診断することに成功した本プロトコルの総合難易度評価は、全部歯列欠損症例や部分歯列欠損においては、臨床使用上十分な予測妥当性を示すことがわかった。(著者抄録)

DOI： 10.2186/ajps.11.355

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Other Link： http://id.ndl.go.jp/bib/030070171

Language：Japanese   Publisher：(公社)日本補綴歯科学会  

目的:日本補綴歯科学会は、補綴歯科治療を必要とする患者の複雑な多様性を評価し、それをもとに難易度分類を行うことを目的に「補綴歯科治療の難易度を測定する多軸診断プロトコル」を作成し、すでに臨床上十分な信頼性を示すことを確認した。本研究では多施設臨床追跡研究により本プロトコルの妥当性を検討した。方法:新たに作成した多軸診断プロトコルは、口腔内の状態、身体社会的状態、口腔関連QOL(OHIP-J54)、精神心理学的状態の4つの診断軸からなる。それぞれグレード0(易しい)から3(難しい)の4段階評価を行う。日本補綴歯科学会の認定研修施設である大学病院補綴科9施設で、歯質もしくは歯列欠損に対し補綴歯科治療が必要と判断された初診患者を連続サンプリングした。補綴歯科治療前に、本プロトコルを用いて難易度評価を行った。そして補綴歯科治療後に、治療に要した時間、医療費などの医療資源および口腔関連QOL評価を行った。本プロトコルの構成概念妥当性は、治療前の術者の主観による難易度評価と、本プロトコルの各軸の難易度の相関を求め検討した。予測妥当性は、総医療費、総治療時間、治療前後の口腔関連QOL変化量をサロゲートエンドポイントとして用い、本プロトコルの4つの診断軸の難易度を統合した総合難易度との相関を求めた。結果と考察:口腔内の状態(Axis I)、身体社会的状態(Axis II)、口腔関連QOL(Axis III)と治療前の術者の主観による難易度評価は、有意な正の相関を示した。一方、精神心理学的状態(Axis IV)と治療前の術者の主観による難易度評価には相関が認められなかった。術前に本プロトコルで評価した患者の総合難易度は、治療の難易度とよく関連すると考えられるサロゲートエンドポイント(総治療費、総治療時間、口腔関連QOL改善量)のいずれとも有意に相関した。口腔内状況別にこの関係を精査すると、術前の総合難易度評価は、全部歯列欠損症例や部分歯列欠損症例においては、これらのサロゲートエンドポイントの一部と有意に相関が認められたが、全部歯列欠損と部分歯列欠損の混合症例や歯の問題の症例においては、それらのサンプルサイズが小さいこともあり有意差が認められなかった。結論:補綴歯科治療の難易度を初めて多軸診断することに成功した本プロトコルの総合難易度評価は、全部歯列欠損症例や部分歯列欠損においては、臨床使用上十分な予測妥当性を示すことがわかった。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J05334&link_issn=&doc_id=20191101190011&doc_link_id=%2Fdv5proso%2F2019%2F001104%2F013%2F0355-0375%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdv5proso%2F2019%2F001104%2F013%2F0355-0375%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

Epithelial keratinization involves complex cellular modifications that provide protection against pathogens and chemical and mechanical injuries. In the oral cavity, keratinized mucosa is also crucial to maintain healthy periodontal or peri-implant tissues. In this study, we investigated the roles of type XVIII collagen, a collagen-glycosaminoglycan featuring an extracellular matrix component present in the basement membrane, in oral mucosal keratinization. Histological analysis of keratinized and non-keratinized oral mucosa showed that type XVIII collagen was highly expressed in keratinized mucosa. Additionally, a 3D culture system using human squamous carcinoma cells (TR146) was used to evaluate and correlate the changes in the expression of type XVIII collagen gene, COL18A1, and epithelial keratinization-related markers, e.g., keratin 1 (KRT1) and 10 (KRT10). The results showed that the increase in COL18A1 expression followed the increase in KRT1 and KRT10 mRNA levels. Additionally, loss-of-function analyses using silencing RNA targeting COL18A1 mRNA and a Col18-knockout (KO) mouse revealed that the absence of type XVIII collagen induces a dramatic decrease in KRT10 expression as well as in the number and size of keratohyalin granules. Together, the results of this study demonstrate the importance of type XVIII collagen in oral mucosal keratinization.

DOI： 10.3390/ijms20194739

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

Global gene deletion studies have established that Runt-related transcription factor-2 (Runx2) is essential during skeletogenesis for osteoblastic differentiation in both intramembranous and endochondral ossification processes. However, the postnatal significance of Runx2 in vivo is poorly understood because a global Runx2 deletion causes perinatal lethality. In this study, we generated tamoxifen-induced Runx2 global deficient mice by crossing Runx2flox mice with ROSA26-CreERT2 mice (Rosa26-CreERT2; Runx2flox/flox). Four-week-old mice were intraperitoneally treated with tamoxifen for five consecutive days, sacrificed, and analyzed six weeks after tamoxifen administration. Deletion of Runx2 led to low bone mass, which is associated with decreased bone formation and bone resorption as well as excessive bone marrow adiposity. Collectively, postnatal Runx2 absolutely plays an important role in maintaining the homeostasis of bone tissues not only in bone mass, but also in the bone marrow environment.

DOI： 10.1016/j.bbrc.2019.07.014

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

OBJECTIVES: To identify significant risk factors associated with incidence of mortality and pneumonia in whole-community-based older inpatients resident in Japanese rural region. METHODS: Patients older than 65 years admitted between 1 April and 15 April 2010 to a core hospital located in a rural region were exhaustively recruited, and incidence of mortality and pneumonia during the 32-month follow-up period were evaluated. Independent variables at baseline measurement included age, gender, body mass index, Charlson comorbidity index, functional dependency, oral self-care ability index, number of remaining teeth, hyposalivation and nutritional status. Dependent variables were incidence of mortality and pneumonia. Survival and non-pneumonia curves were drawn using Kaplan-Meier analysis. Cox proportional hazards analysis was performed to identify the risk factors related to incidence of mortality and pneumonia. RESULTS: The survival rate of 46 patients (male/female: 11/35; mean age: 83.8 ± 6.8 years) was 52.1%, and the incidence of pneumonia was 60.9%. Malnutrition and gender (male) were identified as significant risk factors for mortality (odds ratio [OR]: 8.18 and 4.90; 95% confidence interval [CI]: 1.77-37.3 and 1.50-16.0; P < 0.01 and <0.01, respectively). Loss of oral self-care ability and gender (male) were identified as significant risk factors for incidence of pneumonia (OR: 8.97 and 4.58; 95% CI: 1.70-47.4 and 1.50-14.0; P = 0.01 and <0.01, respectively). CONCLUSIONS: Malnutrition and loss of oral self-care ability were significant risk factors for incidence of mortality and pneumonia, respectively. In response, supplying nutrition with appropriate diet and personalised oral care might contribute to reduction in mortality and prevention of pneumonia.

DOI： 10.1111/ger.12402

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

BACKGROUND: Recent advances in tissue regeneration approaches including 3D organoids, were based on various 3D organogenesis models. However, 3D models are generally technique-sensitive and time-consuming. Thus, we utilized an existing model of submandibular salivary gland (SMG) to modify a simple and highly reproducible in vitro 3D culture model of primary SMG cells self-organization into a well-developed cell spheroid inside Matrigel substrate. We used this model to observe the collective multicellular behavior during spheroid formation. Further, we applied various quantitative approaches including real-time live imaging and immune histochemical image analysis to dissect the cellular dynamics during tissue patterning. RESULTS: On a time-scale of hours, we observed marked size and shape transformations in the developed 3D spheroid which resulted in a spatially-controlled growth differential from the canter to the periphery of the formed aggregates. Moreover, we investigated the effect of fibronectin (FN) on SMG cells self-organization using our simplified culture model. Interestingly, we discovered a novel role of FN in inducing duct-like elongation during initial stages of SMG bud formation. CONCLUSION: This in vitro model provides an excellent tool for analyzing the intercellular dynamics during early SMG tissue development as well as revealing a novel role of FN in SMG ductal expansion.

DOI： 10.1002/dvdy.78

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PURPOSE: We clarified cumulative survival and event-free rates of resin-bonded fixed dental prostheses (RBFDPs) and compared them to those of fixed dental prostheses (FDPs) to refine risk factors for non-survival/event and use of tooth extraction after the period of non-survival/event. METHODS: Study subjects were selected among all patients who consecutively attended the Fixed Prosthodontic Clinic of Okayama University Hospital. Eligible patients were those who received 3-unit metal-framed 2-retainer (wing-wing) RBFDPs or conventional full-coverage FDPs (RBFDPs/FDPs: 129/177 prostheses). Data were analyzed by Kaplan-Meier analysis with the log-rank test, Mann-Whitney test, chi-square test, and Cox proportional hazards analysis. RESULTS: The 15-year cumulative survival rates were 66.5% for the RBFDP group and 61.6% for the FDP group, which were not significantly different (p = 0.59). The 15-year cumulative event-free rates were 53.4% for the RBFDP group and 59.2% for the FDP group, which were not significantly different (p = 0.52). No significant risk factors related to non-survival and event-free of RBFDPs/FDPs were identified in the analysis model using treatment method, sex, age, number of remaining teeth, and treatment site as explanatory variables. The number of cases in which RBFDPs/FDPs resulted in non-survival due to abutment tooth extraction was significantly lower in RBFDPs (p < 0.01). Further, the abutment tooth as a non-vital tooth was identified as a risk factor for RBFDPs/FDPs resulting in non-survival due to abutment tooth extraction. CONCLUSIONS: The present study is the first to indicate RBFDP as a prosthetic treatment option which should be selected for patients with slight or no abutment tooth decay.

DOI： 10.1016/j.jpor.2019.02.004

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

In vitro synthesis of bone tissue has been paid attention in recent years; however, current methods to fabricate bone tissue are still ineffective due to some remaining gaps in the understanding of real in vivo bone formation process, and application of the knowledge in bone synthesis. Therefore, the objectives of this study were first, to perform a systematic and ultrastructural investigation of the initial mineral formation during intramembranous ossification of mouse calvaria from a material scientists' viewpoint, and to develop novel mineralization methods based on the in vivo findings. First, the very initial mineral deposition was found to occur at embryonic day E14.0 in mouse calvaria. Analysis of the initial bone formation process showed that it involved the following distinct steps: collagen secretion, matrix vesicle (MV) release, MV mineralization, MV rupture, and collagen fiber mineralization. Next, we performed in vitro mineralization experiments using MVs and hydrogel scaffolds. Intact MVs embedded in collagen gel did not mineralize, whereas, interestingly, MV nanofragments obtained by ultrasonication could promote rapid mineralization. These results indicate that mechanically ruptured MV membrane can be a promising material for in vitro bone tissue synthesis. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1021-1030, 2019.

DOI： 10.1002/jbm.a.36618

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

A deeper understanding of the detailed mechanism of in vivo tissue healing is necessary for the development of novel regenerative therapies. Among several external factors, environmental pH is one of the crucial parameters that greatly affects enzyme activity and cellular biochemical reactions involving tissue repair and homeostasis. In this study, in order to analyze the microenvironmental conditions during bone healing, we first measured the pH in vivo at the bone healing site using a high-resolution fiber optic pH microsensor directly in femur defects and tooth extraction sockets. The pH was shown to decrease from physiological 7.4 to 6.8 during the initial two days of healing (inflammatory phase). In the same initial stages of the inflammatory phase of the bone healing process, mesenchymal stem cells (MSCs) are known to migrate to the healing site to contribute to tissue repair. Therefore, we investigated the effect of a short-term acidic (pH 6.8) pre-treatment on the stemness of bone marrow-derived MSCs (BMSCs). Interestingly, the results showed that pre-treatment of BMSCs with acidic pH enhances the expression of stem cell markers (OCT-4, NANOG, SSEA-4), as well as cell viability and proliferation. On the other hand, acidic pH decreased BMSC migration ability. These results indicate that acidic pH during the initial stages of bone healing is important to enhance the stem cell properties of BMSCs. These findings may enable the development of novel methods for optimization of stem cell function towards tissue engineering or regenerative medicine.

DOI： 10.3390/ijms20051097

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

The antagonist-specific regulation in tissue engineering constitutes important attempts to achieve an improved and rapid bone regeneration by controlling the natural biological response of the natural body growth factors. L51P is molecularly engineered bone morphogentic protein-2 (BMP-2) variant with a substitution of the 51st leucine with a proline residue. L51P is deficient in BMP receptor binding, but maintains its structure and affinity for inhibitory proteins such as noggin, chordin, and gremlin. These modifications convert the BMP-2 variant L51P into a receptor-inactive inhibitor of BMP antagonists. This current approach may prevent the uncontrolled bone overgrowth using high concentration of BMPs and thus regulates the possible growth factor's high-dose side effects. Exploring of L51P biological functions is required to broad our understanding of BMP mutant biological functions and their potential clinical applications. The progress of L51P researches would hopefully lead to the development of multiple applications for using the L51P in bone and fracture healing disorders.

DOI： 10.1007/s00774-018-0925-0

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

Bone morphogenetic protein 2 (BMP-2) is widely known as a potent growth factor that promotes bone formation. However, an increasing number of studies have demonstrated side effects of BMP-2 therapy. A deeper understanding of the effect of BMP-2 on cells other than those involved directly in bone remodeling is of fundamental importance to promote a more effective delivery of BMP-2 to patients. In this study, we aimed to investigate the effect of BMP-2 in the marrow environment. First, BMP-2 adsorbed onto titanium implants was delivered at the tooth extraction socket (marrow-absent site) or in the mandible marrow of beagle dogs. BMP-2 could induce marked bone formation around the implant at the tooth extraction socket. Surprisingly, however, no bone formation was observed in the BMP-2-coated titanium implants inserted in the mandible marrow. In C57BL/6 mice, BMP-2 adsorbed in freeze-dried collagen pellets could induce bone formation in marrow-absent calvarial bone. However, similar to the canine model, BMP-2 could not induce bone formation in the femur marrow. Analysis of osteoblast differentiation using Col1a1(2.3)-GFP transgenic mice revealed a scarce number of osteoblasts in BMP-2-treated femurs, whereas in the control group, osteoblasts were abundant. Ablation of femur marrow recovered the BMP-2 ability to induce bone formation. In vitro experiments analyzing luciferase activity of C2C12 cells with the BMP-responsive element and alkaline phosphatase activity of MC3T3-E1 osteoblasts further revealed that bone marrow cells inhibit the BMP-2 effect on osteoblasts by direct cell-cell contact. Collectively, these results showed that the effect of BMP-2 in inducing bone formation is remarkably repressed by marrow cells via direct cell-cell contact with osteoblasts; this opens new perspectives on the clarification of the side-effects associated with BMP-2 application. © 2018 American Society for Bone and Mineral Research.

DOI： 10.1002/jbmr.3598

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PURPOSE: This report was written to introduce an attempt at clinical application of our newly developed digital workflow to reproduce the morphology of the subgingival contour and the emergence profile of the provisional restoration within the final bone-anchored fixed restoration, using a bounded unilateral edentulous case. METHODS: This digital workflow involves superimposition of the composite images of two specific types of working casts onto the working cast for the provisional restoration namely, a split cast screwed with a titanium base and a split cast screwed with a provisional restoration and integrating these with the whole intraoral surface image, in which the provisional restoration was present. The final restoration fabricated using this technique could be installed without any clinical problems. The results of in silico analysis revealed that the cubic volume ratio of the total discrepancy between the provisional and the final restorations was only 2.4%. Further, sufficient oral hygiene was maintained and the patient was satisfied with the outcome of the treatment. CONCLUSIONS: This technical report suggests that our newly developed digital workflow provided clinical applicability and may enable accurate transfer of the morphology of the subgingival contour and emergence profile of the provisional to the final bone-anchored fixed restoration.

DOI： 10.1016/j.jpor.2018.10.004

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

Stem cells have essential applications in in vitro tissue engineering or regenerative medicine. However, there is still a need to understand more deeply the mechanisms of stem cell differentiation and to optimize the methods to control stem cell function. In this study, we first investigated the activity of DNA methyltransferases (DNMTs) during chondrogenic differentiation of human bone marrow-derived mesenchymal stem/progenitor cells (hBMSCs) and found that DNMT3A and DNMT3B were markedly upregulated during hBMSC chondrogenic differentiation. In an attempt to understand the effect of DNMT3A and DNMT3B on the chondrogenic differentiation of hBMSCs, we transiently transfected the cells with expression vectors for the two enzymes. Interestingly, DNMT3A overexpression strongly enhanced the chondrogenesis of hBMSCs, by increasing the gene expression of the mature chondrocyte marker, collagen type II, more than 200-fold. Analysis of the methylation condition in the cells revealed that DNMT3A and DNMT3B methylated the promoter sequence of early stem cell markers, NANOG and POU5F1(OCT-4). Conversely, the suppression of chondrogenic differentiation and the increase in stem cell markers of hBMSCs were obtained by chemical stimulation with the demethylating agent, 5-azacitidine. Loss-of-function assays with siRNAs targeting DNMT3A also significantly suppressed the chondrogenic differentiation of hBMSCs. Together, these results not only show the critical roles of DNMTs in regulating the chondrogenic differentiation of hBMSCs, but also suggest that manipulation of DNMT activity can be important tools to enhance the differentiation of hBMSCs towards chondrogenesis for potential application in cartilage tissue engineering or cartilage regeneration.

DOI： 10.1159/000502885

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Language：English   Publisher：WILEY  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry ({RSC})  

Bone is a sophisticated organic-inorganic hybrid material, whose formation involves a complex spatio-temporal sequence of events regulated by the cells. A deeper understanding of the mechanisms behind bone mineralization at different size scales, and using a multidisciplinary approach, may uncover novel pathways for the design and fabrication of functional bone tissue in vitro. The objectives of this study were first to investigate the environmental factors that prime initial mineralization using the secondary ossification center as an in vivo model, and then to apply the obtained knowledge for rapid in vitro synthesis of bone-like tissue. First, the direct and robust measurement of pH showed that femur epiphysis is alkaline (pH ≅ 8.5) at the initial mineral stage at post-natal day 6. We showed that the alkaline milieu is decisive not only for alkaline phosphatase activity, which precedes mineral formation at P6, but also for determining initial mineral precipitation and spherical morphology. Next, engineering approaches were used to synthesize bone-like tissue based on alkaline milieu and artificial chondrocyte membrane nanofragments, previously shown to be the nucleation site for mineral formation. Interestingly, mineralization using artificial cell membrane nanofragments was achieved in just 1 day. Finally, ex vivo culture of femur epiphysis in alkaline pH strongly induced chondrocyte burst, which was previously shown to be the origin of chondrocyte membrane nanofragments, and also enhanced mineral formation. Taken together, these findings not only shed more light on the microenvironmental conditions that prime initial bone formation in vivo, but they also show that alkaline milieu can be used as an important factor for enhancing methods for in vitro synthesis of bone tissue.

DOI： 10.1039/c8tb01544a

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Language：Japanese   Publisher：クインテッセンス出版(株)  

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

Understanding the mechanisms that control cutaneous wound healing is crucial to successfully manage repair of damaged skin. The goal of the current study was to uncover novel extracellular matrix (ECM) components that control the wound healing process. Full thickness skin defects were created in mice and used to show CCN4 up-regulation during wound-healing as early as 1 day after surgery, suggesting a role in inflammation and subsequent dermal migration and proliferation. To determine how CCN4 could regulate wound healing we used Ccn4-KO mice and showed they had delayed wound closure accompanied by reduced expression of Col1a1 and Fn mRNA. Boyden chamber assays using Ccn4-deficient dermal fibroblasts showed they have reduced migration and proliferation compared to WT counterparts. To confirm CCN4 has a role in proliferation and migration of dermal cells, siRNA knockdown and transduction of CCN4 adenoviral transduction were used and resulted in reduced or enhanced migration of human adult dermal fibroblast (hADF) cells respectively. The induced migration of the dermal fibroblasts by CCN4 appears to work via α5β1 integrin receptors that further stimulates down-stream ERK/JNK signaling. The regulation of CCN4 by TNF-α prompted us look further at their potential relationship. Treatment of hADFs with CCN4 and TNF-α alone or together showed CCN4 counteracted the inhibition of TNF-α on COL1A1 and FN mRNA expression and the stimulation of TNF-α on MMP-1 and MMP3 mRNA expression. CCN4 appeared to counterbalance the effects of TNF-α by inhibiting downstream NF-κB/p-65 signaling. Taken together we show CCN4 stimulates dermal fibroblast cell migration, proliferation and inhibits TNF-α stimulation, all of which could regulate wound healing.

DOI： 10.1016/j.matbio.2018.01.004

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Language：Japanese   Publisher：(一社)日本歯科医学教育学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

The antagonist-specific regulation in tissue engineering constitutes important attempts to achieve an improved and rapid bone regeneration by controlling the natural biological response of the natural body growth factors. L51P is molecularly engineered bone morphogentic protein-2 (BMP-2) variant with a substitution of the 51st leucine with a proline residue. L51P is deficient in BMP receptor binding, but maintains its structure and affinity for inhibitory proteins such as noggin, chordin, and gremlin. These modifications convert the BMP-2 variant L51P into a receptor-inactive inhibitor of BMP antagonists. This current approach may prevent the uncontrolled bone overgrowth using high concentration of BMPs and thus regulates the possible growth factor's high-dose side effects. Exploring of L51P biological functions is required to broad our understanding of BMP mutant biological functions and their potential clinical applications. The progress of L51P researches would hopefully lead to the development of multiple applications for using the L51P in bone and fracture healing disorders.

DOI： 10.1007/s00774-018-0925-0

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

PURPOSE: The Japan Prosthodontic Society developed a multi-axis assessment protocol to evaluate the complex variations in patients who need prosthodontic care, and to classify the level of treatment difficulty. A previous report found the protocol to be sufficiently reliable. The purpose of this multi-center cohort study was to evaluate the validity of this multi-axis assessment protocol. METHODS: The treatment difficulty was evaluated using the multi-axis assessment protocol before starting prosthodontic treatment. The time required for active prosthodontic treatment, medical resources such as treatment cost, and changes in the oral health-related QOL before and after treatment, were evaluated after treatment completion. The construct validity of this protocol was assessed by the correlation between the dentist's pre-operative subjective assessment of the treatment difficulty, and the level of difficulty determined by this protocol. The predictive validity was assessed estimating the correlations between a "comprehensive level of treatment difficulty" based on the four axes of this protocol and total treatment cost, total treatment time, and changes in the oral health-related QOL before and after treatment. RESULTS: The construct validity of this protocol was well documented except for psychological assessment. Regarding the predictive validity, the comprehensive level of treatment difficulty assessed before treatment was significantly correlated with the three surrogate endpoints known to be related to the treatment difficulty (total treatment cost, treatment time, and improvement in the oral health-related QOL). To further clarify the validity of the protocol according to patients' oral condition, a subgroup analysis by defects was performed. Analyses revealed that treatment difficulty assessment before treatment was significantly related to one or two surrogate endpoints in the fully edentulous patients and the partially edentulous patients. No significant relationship was observed in the patients with mixture of full/partial edentulism and the patients with teeth problems, possibly due to the small sample size in these groups. CONCLUSION: This study revealed that the multi-axis assessment protocol was sufficiently valid to predict the level of treatment difficulty in prosthodontic care in patients with fully edentulous defects and with partially edentulous defects.

DOI： 10.1016/j.jpor.2017.08.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Keratinized mucosa is of fundamental importance to maintain healthy gingival tissue, and understanding the mechanisms of oral mucosa keratinization is crucial to successfully manage healthy gingiva. Previous studies have shown a strong involvement of the basement membrane in the proliferation and differentiation of epithelial cells. Therefore, first, to identify the keratinized mucosa-specific basement membrane components, immunohistochemical analysis for the six alpha chains of type IV collagen was performed in 8-week-old mice. No difference in the expression pattern of type IV collagen α1(IV) and α2(IV) chains was observed in the keratinized and non-keratinized mucosa. Interestingly, however, type IV collagen α5(IV) and α6(IV) chains specifically were strongly detected in the keratinized mucosa. To analyze the functional roles of the type IV collagen isoform α6(IV) in oral mucosa keratinization, we analyzed Col4a6-knockout mice. Epithelial developmental delay and low levels of KRT10 were observed in new-born Col4a6-knockout mice. Additionally, in vitro experiments with loss-of function analysis using human gingival epithelial cells confirmed the important role of α6(IV) chain in epithelial keratinization. These findings indicate that α112:α556 (IV) network, which is the only network that includes the α6(IV) chain, is one regulator of KRT10 expression in keratinization of oral mucosal epithelium.

DOI： 10.1038/s41598-018-21000-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry ({RSC})  

Analysis of tissue development from multidisciplinary approaches can result in more integrative biological findings, and can eventually allow the development of more effective bioengineering methods. In this study, we analyzed the initial steps of mineral formation during secondary ossification of mouse femur based on biological and bioengineering approaches. We first found that some chondrocytes burst near the mineralized area. External factors that could trigger chondrocyte burst were then investigated. Chondrocyte burst was shown to be modulated by mechanical and osmotic pressure. A hypotonic solution, as well as mechanical stress, significantly induced chondrocyte burst. We further hypothesized that chondrocyte burst could be associated with space-making for mineral expansion. In fact, ex vivo culture of femur epiphysis in hypotonic conditions, or under mechanical pressure, enhanced mineral formation, compared to normal culture conditions. Additionally, the effect of mechanical pressure on bone formation in vivo was investigated by immobilization of mouse lower limbs to decrease the body pressure onto the joints. The results showed that limb immobilization suppressed bone formation. Together, these results suggest chondrocyte burst as a novel fate of chondrocytes, and that manipulation of chondrocyte burst with external mechano-chemical stimuli could be an additional approach for cartilage and bone tissue engineering.

DOI： 10.1039/c7ib00130d

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Biomineralization involves complex processes and interactions between organic and inorganic matters, which are controlled in part by the cells. The objectives of this study were, first, to perform a systematic and ultrastructural investigation of the initial mineral formation during secondary ossification center of mouse femur based on material science and biology viewpoint, and then develop novel biomaterials for mineralization based on the in vivo findings. First, we identified the very initial mineral deposition at postnatal day 5 (P5) at the medial side of femur epiphysis by nanocomputed tomography. Initial minerals were found in the surroundings of hypertrophic chondrocytes. Interestingly, histological and immunohistochemical analyses showed that initial mineralization until P6 was based on chondrocyte activity only, i.e., it occurred in the absence of osteoblasts. Moreover, electron microscopy-based ultrastructural analysis showed that cell-secreted matrix vesicles were absent in the early steps of osteoblast-independent endochondral ossification. Instead, chondrocyte membrane nanofragments were found in the fibrous matrix surrounding the hypertrophic chondrocytes. EDS analysis and electron diffraction study indicated that cell membrane nanofragments were not mineralized material, and could be the nucleation site for the newly formed calcospherites. The phospholipids in the cell membrane nanofragments could be a source of phosphate for subsequent calcium phosphate formation, which initially was amorphous, and later transformed into apatite crystals. Finally, artificial cell nanofragments were synthesized from ATDC5 chondrogenic cells, and in vitro assays showed that these nanofragments could promote mineral formation. Taken together, these results indicated that cell membrane nanofragments were the nucleation site for mineral formation, and could potentially be used as material for manipulation of biomineralization.

DOI： 10.1021/acsbiomaterials.7b00962

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

Whole-organ regeneration has great potential for the replacement of dysfunctional organs through the reconstruction of a fully functional bioengineered organ using three-dimensional cell manipulation in vitro. Recently, many basic studies of whole-tooth replacement using three-dimensional cell manipulation have been conducted in a mouse model. Further evidence of the practical application to human medicine is required to demonstrate tooth restoration by reconstructing bioengineered tooth germ using a postnatal large-animal model. Herein, we demonstrate functional tooth restoration through the autologous transplantation of bioengineered tooth germ in a postnatal canine model. The bioengineered tooth, which was reconstructed using permanent tooth germ cells, erupted into the jawbone after autologous transplantation and achieved physiological function equivalent to that of a natural tooth. This study represents a substantial advancement in whole-organ replacement therapy through the transplantation of bioengineered organ germ as a practical model for future clinical regenerative medicine.

DOI： 10.1038/srep44522

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Language：Japanese   Publisher：Japan Prosthodontic Society  

DOI： 10.2186/ajps.9.303

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Language：Japanese   Publisher：日本歯科医学教育学会  

DOI： 10.24744/jdea.33.3_149

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Language：Japanese   Publisher：(公社)日本矯正歯科学会  

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Language：English   Publisher：FEDERATION AMER SOC EXP BIOL  

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：Institute of Electrical and Electronics Engineers Inc.  

Biological tissues have specific cell patterns and well-organized structures which result from various organogenesis processes. Among which is branching morphogenesis which is the key developmental processes for many glandular tissues including lungs, kidney, salivary gland and liver. Many approaches were suggested to regenerate salivary gland tissue in vitro. Here, we developed a 3D culture technique to study and recapitulate the dynamic forces generated during SMG organogenesis by utilizing time lapse live imaging to monitor the cellular migration and reorganization process of both epithelium and mesenchyme cells.

DOI： 10.1109/MHS.2015.7438259

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORP  

Development of human bodies, organs, and tissues contains numerous steps of cellular differentiation including an initial zygote, embryonic stem (ES) cells, three germ layers, and multiple expertized lineages of cells. Induced pluripotent stem (iPS) cells have been recently developed using defined reprogramming factors such as Nanog, Klf5, Oct3/4 (Pou5f1), Sox2, and Myc. This outstanding innovation is largely changing life science and medicine. Methods of direct reprogramming of cells into myocytes, neurons, chondrocytes, and osteoblasts have been further developed using modified combination of factors such as N-myc, L-myc, Sox9, and microRNAs in defined cell/tissue culture conditions. Mesenchymal stem cells (MSCs) and dental pulp stem cells (DPSCs) are also emerging multipotent stem cells with particular microRNA expression signatures. It was shown that miRNA-720 had a role in cellular reprogramming through targeting the pluripotency factor Nanog and induction of DNA methyltransferases (DNMTs). This review reports histories, topics, and idea of cellular reprogramming.

DOI： 10.1155/2016/7530942

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

OBJECTIVE: The aim of this prospective longitudinal investigation was to compare the relationship between the temporomandibular joint (TMJ) condyles and the temporal fossae by means of tomography before and after the orthodontic correction of Class II, division 1 malocclusion using the activator appliance. MATERIALS AND METHODS: The final sample consisted of 26 consecutively treated Class II, division 1 patients (19 boys and 7 girls with an average pre-treatment age of 11 years) who underwent orthodontic treatment by means of an activator appliance. Before treatment all patients were free of signs and symptoms associated to TMJ disorders. Bilateral tomographic records before and after treatment were taken and analyzed. Outlines of the condyle and temporal fossa were automatically determined by an edge-detection protocol, and the minimum joint space dimension was automatically measured every 2 degrees. For further analysis, the joint space was divided into anterior, superior, and posterior joint spaces. RESULTS: The average treatment time with the activator appliance was 366 days. In all subjects, activator treatment resulted in a Class I dental arch relationship. After activator treatment, no differences were found in the joint space measurements in any direction. Comparisons between the right and left condyles were not significantly different. CONCLUSIONS: Joint space dimension in Class II division I children was similar before and after treatment in both TMJs.

DOI： 10.1093/ejo/cju091

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ALLEN PRESS INC  

DOI： 10.1563/AAID-JOI-D-13-00216

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

PURPOSE: The purpose of this study was to identify the related risk factors of dental implant accumulated postoperative pain and swelling by cellular phone-based assessment. METHODS: Subjects were a consecutive series of patients who received oral implant surgery at Okayama University Hospital. Cellular phone-based questionnaire was sent at pre-set schedule to each subject every 2h on the day of surgery, and every 24h from the 2nd to 7th day post-surgery. Subjects replied in real-time the pain and swelling levels at the operated sites by an 11- and 4-grade rating-scale questionnaire. Overall intensity of individual pain and swelling was calculated by means of area under curve that drew by their time-dependent changes. Predictor variables were age, gender, presence of diabetes mellitus and/or hypertension (DM/HT), history of implant surgery, number of inserted implants, flap operation, surgical duration, pre-surgery anxiety, osteoplasty, bone quality, premedication, dosage of prescribed analgesics and local anesthesia and accumulated postoperative pain/swelling. Compliance rate and risk factors correlated with accumulated postoperative pain and swelling were calculated by multiple regression analysis. RESULTS: Final subjects were 18 females and 7 male (mean age: 59.3±7.32 yrs). Significant factors correlated with accumulated postoperative pain were DM/HT, surgical duration, premedication, bone quality, pre-surgery anxiety and postoperative swelling (R(2)=0.769, p=0.001, 0.013, 0.032, 0.007, 0.035 and 0.007, respectively). Meanwhile, significant factors associated with postoperative swelling were postoperative pain, DM/HT and bone quality (R(2)=0.365, p=0.002, 0.004, 0.008, respectively). CONCLUSION: These results suggested DM/HT and bone quality are correlated to overall intensity of postoperative pain and swelling.

DOI： 10.1016/j.jpor.2015.05.003

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Language：Japanese   Publisher：(一社)日本歯科医学教育学会  

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In vitro fabricated biological tissue would be a valuable tool to screen newly synthesized drugs or understand the tissue development process. Several studies have attempted to fabricate biological tissue in vitro. However, controlling the growth and morphology of the fabricated tissue remains a challenge. Therefore, new techniques are required to modulate tissue growth. RGD (arginine-glycine-aspartic acid), which is an integrin-binding domain of fibronectin, has been found to enhance cell adhesion and survival; it has been used to modify substrates for in vitro cell culture studies or used as tissue engineering scaffolds. In addition, this study shows novel functions of the RGD peptide, which enhances tissue growth and modulates tissue morphology in vitro. When an isolated submandibular gland (SMG) was cultured on an RGD-modified alginate hydrogel sheet, SMG growth including bud expansion and cleft formation was dramatically enhanced. Furthermore, we prepared small RGD-modified alginate beads and placed them on the growing SMG tissue. These RGD-modified beads successfully induced cleft formation at the bead position, guiding the desired SMG morphology. Thus, this RGD-modified material might be a promising tool to modulate tissue growth and morphology in vitro for biological tissue fabrication.

DOI： 10.1038/srep11468

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

Aggressive periodontitis is a great challenge to clinicians when providing orthodontic treatment because of the potential for progression of periodontal disease. In this article, we report the successful comprehensive orthodontic treatment of bimaxillary protrusion and severe crowding in an adult with generalized aggressive periodontitis. A woman, aged 22 years 7 months, with a chief complaint of incisal crowding was diagnosed with a skeletal Class I malocclusion associated with severe anterior crowding, possibly worsened by generalized aggressive periodontitis. In addition to a periodontal examination, a blood IgG antibody titer analysis and microbiologic examination for periodontal pathogens were used to diagnose the type of periodontal disease and determine the proper timing to initiate orthodontic treatment. The total active treatment period was 28 months, followed by periodontal prostheses and regeneration therapy. Consequently, satisfactory facial profile, occlusion, and periodontal health were maintained for at least 36 months. These results indicate that efficient screening is important for providing successful orthodontic treatment in patients with advanced periodontal disease. This report also demonstrates the diagnostic importance of blood IgG antibody titer assays and microbiologic examinations to detect periodontal pathogens.

DOI： 10.1016/j.ajodo.2014.09.022

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

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

PURPOSE: The aim of this article was to investigate the accuracy in the reproducibility of full-arch implant provisional restorations to final restorations between a 3D Scan/CAD/CAM technique and the conventional method. METHODS: We fabricated two final restorations for rehabilitation of maxillary and mandibular complete edentulous area and performed a computer-based comparative analysis of the accuracy in the reproducibility of the provisional restoration to final restoration between a 3D scanning and CAD/CAM (Scan/CAD/CAM) technique and the conventional silicone-mold transfer technique. Final restorations fabricated either by the conventional or Scan/CAD/CAM method were successfully installed in the patient. The total concave/convex volume discrepancy observed with the Scan/CAD/CAM technique was 503.50mm(3) and 338.15 mm(3) for maxillary and mandibular implant-supported prostheses (ISPs), respectively. On the other hand, total concave/convex volume discrepancy observed with the conventional method was markedly high (1106.84 mm(3) and 771.23 mm(3) for maxillary and mandibular ISPs, respectively). CONCLUSIONS: The results of the present report suggest that Scan/CAD/CAM method enables a more precise and accurate transfer of provisional restorations to final restorations compared to the conventional method.

DOI： 10.1016/j.jpor.2014.12.001

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Language：Japanese   Publisher：(一社)日本顎関節学会  

目的:多施設にて咬合違和感を訴える患者に関するデータ収集を行い、その実態を調査することを目的とした。対象および方法:各施設を受診した咬合違和感を訴える患者202症例中、調査票で転帰が明らかな180症例を対象とした。患者調査票を作成し、受診までの項目(性別、年齢、病悩期間、主訴の分類、咬合違和感を感じる歯、咬合違和感を感じる部位、咬合違和感を感じる歯の状態、前医でこれまでに受けた治療法)について分析した。結果:性別では男性37名、女性143名で女性に多かった。年齢の中央値(25パーセンタイル、75パーセンタイル)は55.0(42.0、65.0)歳であった(18〜86歳)。また病悩期間の中央値は5(1、13)ヵ月で発症後6ヵ月未満が著明に多かった(発症直後〜360ヵ月)。主訴は「咬頭嵌合位の歯の接触状態に関する訴え」が最も多かった。咬合違和感を感じる歯は大臼歯が多かったが前歯にも認められた。咬合違和感を感じる部位では片側だけでなく、両側の場合などさまざまであったが、全体的に感じる患者も多かった。咬合違和感を感じる歯の状態は金属の補綴装置を装着されている場合が多かったが、天然歯の場合も多かった。前医で行われた治療は補綴歯科治療が多かった。結語:性別、年齢などはいままでの報告と同様であったが、病悩期間はやや異なっていた。また患者は、さまざまな部位で治療後の歯だけでなく天然歯にも違和感を感じていた。(著者抄録)

DOI： 10.11246/gakukansetsu.26.196

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2014&ichushi_jid=J02499&link_issn=&doc_id=20150205190003&doc_link_id=10.11246%2Fgakukansetsu.26.196&url=https%3A%2F%2Fdoi.org%2F10.11246%2Fgakukansetsu.26.196&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PUBLIC LIBRARY SCIENCE  

We herein describe a novel procedure for dentin regeneration that mimics the biological processes of tooth development in nature. The canonical Wnt signaling pathway is an important regulator of the Dentin sialophosphoprotein (Dspp) expression. Our approach mimics the biological processes underlying tooth development in nature and focuses on the activation of canonical Wnt signaling to trigger the natural process of dentinogenesis. The coronal portion of the dentin and the underlying pulp was removed from the first molars. We applied lithium chloride (LiCl), an activator of canonical Wnt signaling, on the amputated pulp surface to achieve transdifferentiation toward odontoblasts from the surrounding pulpal cells. MicroCT and microscopic analyses demonstrated that the topical application of LiCl induced dentin repair, including the formation of a complete dentin bridge. LiCl-induced dentin is a tubular dentin in which the pulp cells are not embedded within the matrix, as in primary dentin. In contrast, a dentin bridge was not induced in the control group treated with pulp capping with material carriers alone, although osteodentin without tubular formation was induced at a comparatively deeper position from the pulp exposure site. We also evaluated the influence of LiCl on differentiation toward odontoblasts in vitro. In the mDP odontoblast cell line, LiCl activated the mRNA expression of Dspp, Axin2 and Kallikrein 4 (Klk4) and downregulated the Osteopontin (Osp) expression. These results provide a scientific basis for the biomimetic regeneration of dentin using LiCl as a new capping material to activate dentine regeneration.

DOI： 10.1371/journal.pone.0121938

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Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：FEDERATION AMER SOC EXP BIOL  

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

Bone morphogenetic protein 2 (BMP2) is a potent osteoinductive cytokine that plays crucial roles in bone repair. However, large amounts of BMP2 are required to induce sufficient bone formation in humans possibly due to a feedback response of BMP antagonists. The engineered BMP2 variant L51P is deficient in BMP receptor type I activation but maintains affinity for BMP antagonists and can allow for the inactivation of BMP antagonists, and eventually enhance BMP2 action. As hypothesized, simultaneous addition of L51P enhanced the BMP2-induced osteogenesis. To test the ability of L51P to competitively inactivate BMP antagonists, cell binding affinity of BMP2 ligands was investigated in the presence or absence of L51P. Because the BMP antagonists were highly expressed 3 days after exogenous BMP2 stimulation, we collected supernatants from 3-day stimulated cell cultures and used as condition culture media (CM). The results showed a significant decrease in the cell binding of BMP2 ligands when cells were incubated with exogenous BMP2 and CM, whereas L51P addition competitively rescued the suppression of BMP2-to-cell binding induced by CM incubation. In a delayed experimental model, L51P was applied 3 days after exogenous BMP2 stimulation and we could observe a striking enhancement of the BMP2-induced SMAD-1/5/8 phosphorylation and luciferase activity of the Id1 promoter compared to the simultaneous addition of the two factors. These findings provide a deeper insight into the cellular and molecular mechanisms involved in the effect of L51P in suppressing the BMP antagonists and enhancing BMP activity. Additionally, these results demonstrate that L51P is a promising down regulator of BMP-induced negative feedback, which could have a significant impact in future applications of BMP2 in research and clinical settings.

DOI： 10.1016/j.bone.2014.09.011

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

PURPOSE: The aim of this study was to evaluate the correlation between sleep bruxism (SB) frequency and serotonin transporter (SERT)-driven serotonin (5-HT)-uptake in platelets. METHODS: Subjects were dental trainee residents and faculty members of Okayama University Hospital who were aware of having severe or no SB. SB frequency was assessed for 3-consecutive nights by a self-contained electromyographic detector/analyzer, which indicated individual SB levels as one of four grades (score 0, 1, 2 and 3). Subjects were classified as normal control (NC) when SB scores indicated only 0 or 1 during the 3 nights, or as severe SB for scores 2 or 3. Those subjects whose scores fluctuated from 0 to 3 during the 3 nights were omitted from further analysis. Fasting peripheral venous blood samples were collected in the morning following the final SB assessment. Amounts of SERTs proteins collected from peripheral platelets were quantified using ELISA, and SERTs transport activity was assessed by uptake assay using [3H]-5-HT. RESULTS: Thirteen severe SB subjects and 7 NC subjects were eligible. Gender distribution, mean age, 5-HT concentration and total amounts of SERT protein in platelets showed no significant differences between NC and severe SB (p=0.85: Chi-squared test; p=0.64, 0.26, 0.46: t-test). However, [3H]-5-HT uptake by platelets was significantly greater in NC compared to severe SB subjects (12.79±1.97, 8.27±1.91 fmol/10(5) platelets/min, p<0.001, t-test). CONCLUSION: The results of this pilot study suggest a possible correlation between peripheral platelet serotonin transporter uptake ability and SB severity.

DOI： 10.1016/j.jpor.2014.06.003

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

OBJECTIVE: The bonding potential of 'mild' self-etch adhesives may be compromised due to smear interference, as they may not dissolve/penetrate the smear layer effectively due to their relatively low acidity. We observed that the thickness of the dentin smear layer differed depending on the surface-preparation methodology used. METHODS: The interaction of an (ultra-)mild self-etch adhesive (Clearfil S3 Bond, Kuraray Noritake) with human dentin, prepared either using a medium-grit diamond bur ('thick', clinically relevant smear layer) or 600-grit SiC-paper ('thin' smear layer), or just fractured (smear-free), was evaluated using high-resolution transmission electron microscopy (TEM). Non-demineralized/demineralized 30-100nm interfacial cross-sections were prepared following common TEM-specimen processing and diamond-knife ultra-microtomy. RESULTS: The adhesive did not dissolve the bur-cut, nor the SiC-ground smear layer, but impregnated it. Within this 'resin-smear complex', hydroxyapatite was abundantly present. At fractured dentin, this complex was not present, while the actual layer of interaction of the adhesive was limited to about 100nm. Non-demineralized 'ultra-thin' (30-50nm) sections confirmed the interfacial ultra-structure to differ for the three surface-preparation methods. An electron dense band was consistently disclosed at the adhesive interface, most likely representing the documented chemical interaction of the functional monomer 10-MDP with Ca. SIGNIFICANCE: The dentin surface-preparation method significantly affects the nature of the smear layer and the interaction with the ultra-mild self-etch adhesive.

DOI： 10.1016/j.dental.2014.07.006

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Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy.

DOI： 10.1038/srep06044

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Language：Japanese   Publisher：(一社)日本顎関節学会  

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

In an attempt to find out a new molecular counterpart of CCN family protein 2 (CCN2), a matricellular protein with multiple functions, we performed an interactome analysis and found fibroblast growth factor (FGF) -1 as one of the candidates. Solid-phase binding assay indicated specific binding between CCN2 and FGF-1. This binding was also confirmed by surface plasmon resonance (SPR) analysis that revealed a dissociation constant (Kd) of 3.98 nM indicating strong molecular interaction between the two. RNA analysis suggested that both FGF-1 and CCN2 could be produced by chondrocytes and thus their interaction in the cartilage is possible. These findings for the first time indicate the direct interaction of CCN2 and FGF-1 and suggest the co-presence of these molecules in the cartilage microenvironment. CCN2 is a well-known promoter of cartilage development and regeneration, whereas the physiological and pathological role of FGF-1 in cartilage mostly remains unclear. Biological role of FGF-1 itself in cartilage is also suspected.

DOI： 10.1007/s12079-014-0232-z

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

INTRODUCTION: During normal pulp tissue healing, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) or interleukins, act in the initial 48 hours (inflammatory phase) and play important roles not only as chemo-attractants of inflammatory cells and stem/progenitor cells but also in inducing a cascade of reactions toward tissue regeneration or reparative dentin formation or both. Previous reports have shown that inflammatory cytokines regulate the differentiation capacity of dental pulp stem/progenitor cells (DPCs), but none has interrogated the impact of these cytokines on the stem cell phenotype of stem/progenitor cells. This study investigated the effects of a short-term treatment with TNF-α on the stem cell phenotype and differentiation ability of human DPCs. METHODS: An in vivo mouse model of pulp exposure was performed for analysis of expression of the mesenchymal stem cell marker CD146 in DPCs during the initial stage of inflammatory response. For in vitro studies, human DPCs were isolated and incubated with TNF-α for 2 days and passaged to eliminate TNF-α completely. Analysis of stem cell phenotype was performed by quantification of cells positive for mesenchymal stem cell markers SSEA-4 (stage-specific embryonic antigen 4) and CD146 by flow cytometry as well as by quantitative analysis of telomerase activity and mRNA levels of OCT-4 and NANOG. Cell migration, colony-forming ability, and differentiation toward odontogenesis and adipogenesis were also investigated. RESULTS: The pulp exposure model revealed a strong staining for CD146 during the initial inflammatory response, at 2 days after pulp exposure. In vitro experiments demonstrated that a short-term (2-day) treatment of TNF-α increased by twofold the percentage of SSEA-4+ cells. Accordingly, STRO-1, CD146, and SSEA-4 protein levels as well as OCT-4 and NANOG mRNA levels were also significantly upregulated upon TNF-α treatment. A short-term TNF-α treatment also enhanced DPC function, including the ability to form cell colonies, to migrate, and to differentiate into odontogenic and adipogenic lineages. CONCLUSIONS: A short-term treatment with TNF-α enhanced the stem cell phenotype, migration, and differentiation ability of DPCs.

DOI： 10.1186/scrt420

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

In this study we performed a microRNA (miRNA) array to characterize a stem cell population from human dental pulp-derived mesenchymal stromal cells (hDPSCs). miRNA-720 was found to regulate the stem cell phenotype of hDPSCs by targeting the pluripotency factor NANOG.

DOI： 10.1109/MHS.2014.7006080

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DOI： 10.1177/0022034514549377

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

Several preclinical studies have shown that Escherichia coli-derived bone morphogenetic protein-2 (E-BMP-2) is as effective as mammalian cell-derived bone morphogenetic protein-2 (C-BMP-2) in the treatment of bone defects. However, further investigation of the effectiveness and determination of the optimal dosage of E-BMP-2 in large animals are still necessary before its full application in humans. This study investigated the efficiency of different concentrations of E-BMP-2 adsorbed in β-TCP for bone augmentation and osseointegration of immediate dental implants in a swine socket lift model. Following exposure of the maxillary sinus lateral wall, a 3.4-mm (diameter) cavity was drilled and filled with 0.1 g of β-TCP containing different doses of E-BMP-2 (0, 10, 30, or 100 μg/site) to lift the Schneiderian membrane. A dental implant was then immediately inserted. Bone-to-implant contact (BIC) and bone density (BD) examined via histological analysis were used as parameters to assess E-BMP-2 efficiency in bone formation. The implant stability quotient (ISQ) was measured using Osstell to determine the effect of E-BMP-2/β-TCP on implant stability. After 8 weeks, the groups that received 30 and 100 μg of E-BMP-2 showed substantial new bone formation in the elevated space, while no bone formation was observed with β-TCP alone. Accordingly, BIC and BD presented a dose-dependent response to increasing doses of E-BMP-2. However, there was no increase in implant stability with E-BMP-2 treatment. In conclusion, the E-BMP-2/β-TCP combination was efficient in bone formation and osseointegration of dental implants in a socket lift model in mini-pigs.

DOI： 10.1159/000369061

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Publishing type：Research paper (scientific journal)   Publisher：Stem Cell Biology and Tissue Engineering in Dental Sciences  

DOI： 10.1016/B978-0-12-397157-9.00068-0

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Language：Japanese  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：8  

OBJECTIVES: A dental adhesive without small and hydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) would be beneficial in order to avoid contact allergies. However, these monomers are important to increase infiltration and polymerization of the adhesive. Therefore, the purpose of this study was to evaluate the bonding effectiveness and bond durability of a more hydrophobic and biocompatible adhesive as compared to a conventional three-step etch-and-rinse adhesive. METHODS: Sixteen non-carious human third molars were used to determine the micro-tensile bond strength testing (μTBS) and interfacial ultrastructure by transmission electron microscopy (TEM) of the more hydrophobic cmf adhesive system (Saremco) adhesive as compared to the control OptiBond FL (Kerr). RESULTS: The more hydrophobic and biocompatible three-step etch-and-rinse adhesive was able to produce a reasonable short-time bonding effectiveness. In the long term, the collagen fibrils in the hybrid layer were not effectively protected and were prone to hydrolytic degradation. As a result, long-term bonding effectiveness of this novel adhesive was very low. CONCLUSIONS: Application of a more hydrophobic adhesive without altering the application procedure considerably results in a reduced durability of the created bond CLINICAL RELEVANCE: Omitting small and hydrophilic components from the adhesive formulation may impair the durability of your composite restoration.

DOI： 10.1007/s00784-012-0884-0

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Language：Japanese  

DOI： 10.2186/ajps.5.281

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2013&ichushi_jid=J05334&link_issn=&doc_id=20140130250005&doc_link_id=%2Fdv5proso%2F2013%2F000503%2F005%2F0281-0290%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdv5proso%2F2013%2F000503%2F005%2F0281-0290%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/μl was able to induce strong CCN2 expression while a minimum concentration of 25 ng/μl was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme.

DOI： 10.1016/j.archoralbio.2013.08.010

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Language：Japanese   Publisher：(公社)日本矯正歯科学会  

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Language：English   Publisher：(公社)日本生化学会  

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Language：Japanese   Publisher：中・四国矯正歯科学会  

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Language：Japanese   Publisher：岡山歯学会  

Web媒体のデモンストレーション動画配信システム(Web Class)を歯学部学生の固定性架工義歯学基礎実習に導入し、教育効果に与える影響について検討した。対象はWeb Class導入前の歯学部4年次学生59名と導入後の65名である。実習期間にWeb Classを利用した総回数は1132回、総利用時間は207時間28分で、1人当りの平均利用時間は3時間12分であった。Web Class導入前後で、学生の技能習得の向上が認められた。導入後のアンケートにおいて、Web Classは実習を行う上で非常に有益、いくらか有益と回答したのはそれぞれ69%、31%で、予習に活用できた、イメージトレーニングやシミュレーションをするのに役立った、などの意見があった。

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

CCN family proteins 2 and 3 (CCN2 and CCN3) belong to the CCN family of proteins, all having a high level of structural similarity. It is widely known that CCN2 is a profibrotic molecule that mediates the development of fibrotic disorders in many different tissues and organs. In contrast, CCN3 has been recently suggested to act as an anti-fibrotic factor in several tissues. This CCN3 action was shown earlier to be exerted by the repression of the CCN2 gene expression in kidney tissue, whereas different findings were obtained for liver cells. Thus, the molecular action of CCN3 yielding its anti-fibrotic effect is still controversial. Here, using a general model of fibrosis, we evaluated the effect of CCN3 overexpression on the gene expression of all of the CCN family members, as well as on that of fibrotic marker genes. As a result, repression of CCN2 gene expression was modest, while type I collagen and α-smooth muscle actin gene expression was prominently repressed. Interestingly, not only CCN2, but also CCN4 gene expression showed a decrease upon CCN3 overexpression. These findings indicate that fibrotic gene induction is under the control of a complex molecular network conducted by CCN family members functioning together.

DOI： 10.1007/s12079-012-0180-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER  

A significant number of natural compounds have been shown to regulate the behavior of the cells, in collaboration with cellular proteins. CCN2/connective tissue growth factor (CTGF) has been reported to have essential roles in cartilage development, chondrocyte proliferation and differentiation as well as regulation of the extracellular matrix metabolism. Previous studies demonstrated the capability of CCN2 to regenerate surgical defects in articular cartilage of rat knee. Also, transgenic mice over-expressing cartilage-specific CCN2 were shown to be more resistant to aging-related cartilage degradation. We hypothesized that small molecules that induce CCN2 in chondrocytes could be novel candidates to increase the resistance to aging-related cartilage degradation, or even to correct cartilage degenerative changes incurred in OA. Therefore, this study screened a compound library and identified the β-carboline alkaloid harmine as a novel inducer of CCN2 in human chondrocytic HCS-2/8 cells and osteoarthritic articular chondrocytes. Harmine increased the expression of the cartilage markers aggrecan and COL2α1, as well as that of the master regulator of chondrogenesis, SOX-9. Moreover, harmine notably induced chondrogenesis of prechondrocytic ATDC5 cells in micromass cultures. The chondroprotective effect of harmine was investigated under inflammatory condition by stimulation with TNFα, and harmine was shown to ameliorate TNFα-induced decrease in expression of CCN2 and cartilage markers. These findings uncover novel chondrogenic effects of harmine and indicate harmine as a potential drug for prevention and/or repair of cartilage degradation.

DOI： 10.1016/j.biochi.2012.10.016

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

OBJECTIVE: Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria. MATERIALS AND METHODS: First, the osteoinductive effect of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 μg/μl) was applied for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and histology. RESULTS: Release-profile testing showed that PLGA membrane could retain 94% of the initially applied E-BMP-2. Ectopic bone formation assay revealed that combination of E-BMP-2/PLGA membrane strongly induced bone formation. Stronger osteoinductivity with complete repair of critical-sized defects was observed only with PLGA membranes adsorbed with 5 and 10 μg/μl of E-BMP-2, whereas no bone formation was observed in the groups that received no membrane or 0-μg/μl dose of E-BMP-2. CONCLUSION: PLGA membrane was shown to be a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA membrane combination was demonstrated to be efficient in bone regeneration in a model of critical-sized defects.

DOI： 10.1159/000356947

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

Small, self-contained electromyographic (EMG) detector/analyzer (D/A) devices have become available for the detection of jaw muscle activity events above threshold. These devices claim to be less intrusive to the subjects sleep so it is less prone to induce disturbed sleep. The objective of this study was to evaluate for night-to-night variability and examine for a systematic alteration on the first night in EMG levels.
Ten asymptomatic healthy volunteers (mean age, 26.8 +/- 3.78) were recorded for six sequential nights in their home environment using EMG D/A system. The device yields a nightly EMG level above threshold score on a 0-4 level. Because the data are categorical and nonparametric, the data of the ten subjects across six nights were submitted to a Friedman repeated measures ANOVA. The significant level was set as alpha equal to 0.05.
The median and mode values of the subjects were tabulated and analyzed and we did not find a significant difference in EMG D/A level across the six nights (p = 0.287, Kendall's coefficient of concordance = 0.124, Friedman two-way repeated measures ANOVA). The data did show clear and substantial night-to-night variability.
Substantial night-to-night variability in masseter EMG activity levels was clearly observed in our subjects. There was no evidence of a suppressed or elevated first-night effect-like variability on masseter muscle EMG level seen in these subjects using a small portable self-contained EMG detector/analyzer. These data suggest that recordings should be at least 5-6-nights duration to establish a reasonable measure of an individual's average nightly masseter EMG level.

DOI： 10.1007/s11325-011-0602-1

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This educational trial was an eight-day problem-based learning (PBL) course for fourth-year predoctoral students at Okayama University's dental school who interviewed elderly residents living in a nursing home. The purpose of this PBL course was to introduce geriatric dentistry to the students by allowing them, independently, to discover the clinical problems of elderly patients as well as the solutions. The sixty-five students were divided into nine small groups and received patient information (age, gender, degree of care needed, medical history, food type, medications, and oral condition) in datasheets before visiting the nursing home. Each group of students directly interviewed one patient and the caregivers and identified the patient's medical, psychological, and social problems. After the interview, the students participated in a PBL tutorial to delineate a management approach for the patient's problems. To measure the efficacy of this program, the students completed a questionnaire before and after the course regarding their level of understanding of and attitudes toward geriatric dentistry, clinical research, and self-study. The results showed that student's perceptions of their knowledge about and attitudes toward oral health care for the elderly significantly increased after the PBL course, which suggests that such tutorials should be an option for dental curricula.

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

PURPOSE: Small, self-contained electromyographic (EMG) detector/analyzer (D/A) devices have become available for the detection of jaw muscle activity events above threshold. These devices claim to be less intrusive to the subjects sleep so it is less prone to induce disturbed sleep. The objective of this study was to evaluate for night-to-night variability and examine for a systematic alteration on the first night in EMG levels. METHODS: Ten asymptomatic healthy volunteers (mean age, 26.8 ± 3.78) were recorded for six sequential nights in their home environment using EMG D/A system. The device yields a nightly EMG level above threshold score on a 0-4 level. Because the data are categorical and nonparametric, the data of the ten subjects across six nights were submitted to a Friedman repeated measures ANOVA. The significant level was set as alpha equal to 0.05. RESULTS: The median and mode values of the subjects were tabulated and analyzed and we did not find a significant difference in EMG D/A level across the six nights (p = 0.287, Kendall's coefficient of concordance = 0.124, Friedman two-way repeated measures ANOVA). The data did show clear and substantial night-to-night variability. CONCLUSION: Substantial night-to-night variability in masseter EMG activity levels was clearly observed in our subjects. There was no evidence of a suppressed or elevated first-night effect-like variability on masseter muscle EMG level seen in these subjects using a small portable self-contained EMG detector/analyzer. These data suggest that recordings should be at least 5-6-nights duration to establish a reasonable measure of an individual's average nightly masseter EMG level.

DOI： 10.1007/s11325-011-0602-1

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

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

DOI： 10.1016/j.jpor.2012.10.002

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

PURPOSE: Current clinical procedures to control or regenerate bone loss due to peri-implantitis are not predictable neither accomplish complete resolution. Therefore, early detection of the onset and the active periods of bone loss are crucial for prevention of extensive peri-implant bone resorption. This study aimed to determine a possible association between the presence of collagenases (MMP-1, MMP-8 and MMP-13) in peri-implant sulcular fluid (PISF) and active periods of bone loss by annually adjusted vertical bone loss (AVBL) measurements. METHODS: Intended sample consisted of 76 consecutive patients who received oral implant treatment at the Fixed Prosthodontic Clinic of Okayama University Hospital from 1990 to 2000. Twelve subjects were lost to follow-up or refused to participate. Consequently, the actual sample consisted of 64 patients who were followed-up for at least one year. Those patients with AVBL>0.6mm were included in the severe peri-implantitis group, and randomly selected, age-, gender- and implantation site-matched healthy patients (AVBL<0.3mm) comprised the control group. PISF samples were collected from both groups and further analyzed by western blot for detection of collagenases. RESULTS: Four patients presented severe peri-implantitis. MMP-8 was the only collagenase detected in peri-implant sites with ongoing bone loss. PISF samples from control group showed no positive reactions to any collagenase. CONCLUSION: This study showed MMP-8 as a possible marker for progressive bone loss in peri-implantitis.

DOI： 10.1016/j.jpor.2012.07.002

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

Purpose: Current clinical procedures to control or regenerate bone loss due to peri-implantitis are not predictable neither accomplish complete resolution. Therefore, early detection of the onset and the active periods of bone loss are crucial for prevention of extensive pen-implant bone resorption. This study aimed to determine a possible association between the presence of collagenases (MMP-1, MMP-8 and MMP-13) in peri-implant sulcular fluid (PISF) and active periods of bone loss by annually adjusted vertical bone loss (AVBL) measurements.
Methods: Intended sample consisted of 76 consecutive patients who received oral implant treatment at the Fixed Prosthodontic Clinic of Okayama University Hospital from 1990 to 2000. Twelve subjects were lost to follow-up or refused to participate. Consequently, the actual sample consisted of 64 patients who were followed-up for at least one year. Those patients with AVBL &gt; 0.6 mm were included in the severe peri-implantitis group, and randomly selected, age-, gender- and implantation site-matched healthy patients (AVBL &lt;0.3 mm) comprised the control group. PISF samples were collected from both groups and further analyzed by western blot for detection of collagenases.
Results: Four patients presented severe peri-implantitis. MMP-8 was the only collagenase detected in pen-implant sites with ongoing bone loss. PISF samples from control group showed no positive reactions to any collagenase.
Conclusion: This study showed MMP-8 as a possible marker for progressive bone loss in peri-implantitis. (C) 2012 Japan Prosthodontic Society. Published by Elsevier Ireland. All rights reserved.

DOI： 10.1016/j.jpor.2012.07.002

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Language：Japanese   Publisher：(公社)日本矯正歯科学会  

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Language：Japanese   Publisher：中・四国矯正歯科学会  

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

BACKGROUND: The mechanism of tooth development is a complex process regulated by numerous genes including transcription factors, growth factors, and other intra- and extracellular molecules. Especially, transcription factors play a central role in gene expression, regulating a wide spectrum of biological processes including organogenesis. Substantial evidence has been demonstrated by a number of studies using genetically engineered animal models. However, detailed molecular mechanisms of tooth development have not been completely elucidated, partially because numerous genes that play essential roles in tooth development remain unidentified. RESULTS: In this study, we conducted an expression-based screening using gene expression database and in situ hybridization assays. Based on the gene expression database "EMBRYS," 207 out of 1,520 genes were expressed in the maxillary and/or mandibular processes and thus were selected for further analysis by section in situ hybridization. Among these candidates, 28 genes were newly identified as potential factors associated with tooth development by in situ hybridization assays with frontal sections of embryonic day 13.5 and 14.5 mouse embryos. The expression patterns were also examined at embryonic day 16.5 and 18.5. CONCLUSIONS: These results will contribute to elucidating the mechanisms of tooth development and to improving the technology for regeneration of tooth.

DOI： 10.1002/dvdy.23808

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Language：English   Publisher：(一社)日本骨代謝学会  

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OBJECTIVES: Self-etch adhesives are well adopted in general practice, obviously primarily thanks to their ease of use and fast application time. Nevertheless, phosphoric acid is still often recommended to beforehand etch enamel following a so-called 'selective' enamel-etch technique, this in particular when most cavity margins end in enamel. The purpose of this study was to test if a new one-step adhesive can be applied in a multi-mode manner, this following different, either 'full' or 'selective', self-etch and etch-and-rinse approaches. Specific research hypotheses tested were that prior phosphoric-acid etching did not affect the bonding effectiveness of the one-step adhesive to enamel and dentine, and that the bonding effectiveness to dentine was also not affected when the adhesive was applied either following a 'dry-bonding' or 'wet-bonding' etch-and-rinse technique. METHODS: The micro-tensile bond strength (μTBS) of the one-step self-etch adhesive G-Bond Plus (GC, Tokyo, Japan; 1-SEA) was measured when it was bonded to bur-cut enamel following either a 'self-etch' or an 'etch-and-rinse' adhesive protocol, and to bur-cut dentine when applied following either a 'self-etch', a 'dry-bonding' or a 'wet-bonding' etch-and-rinse adhesive protocol. Bond-strength testing was corroborated by ultra-structural analysis of the interfacial interaction at enamel and dentine using transmission electron microscopy (TEM). RESULTS: Prior phosphoric-acid etching significantly increased the bonding effectiveness of the 1-SEA to enamel. A clearly enhanced micro-retentive surface was revealed by TEM. To dentine, no statistically significant difference in bonding effectiveness was recorded when the 1-SEA was either applied following a self-etch or both etch-and-rinse approaches. The 'dry-bonding' etch-and-rinse protocol was significantly more effective than its 'wet-bonding' version. TEM however revealed indications of low-quality hybridisation following both etch-and-rinse approaches, in particular in the form of a porous and poorly resin-infiltrated collagen mesh. CONCLUSIONS: While phosphoric-acid etching definitely improved bonding of the one-step self-etch adhesive to enamel, one should be more careful with additional phosphoric-acid etching of dentine. Although the bond strength was not reduced, the resultant adhesive interface appeared ultra-structurally more vulnerable to biodegradation.

DOI： 10.1016/j.jdent.2012.02.012

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The purpose of the present study was to examine what dysphagic signs identified by videoendoscopy (VE) could predict the incidence of pneumonia and body weight loss in elderly patients living in nursing homes. This study was performed at six nursing care facilities in Japan from March 2007 to February 2009. The 148 subjects (85·1±8·0years, male/female: 43/105) were evaluated for their feeding and swallowing movements by clinical and VE examinations during the consumption of a regular meal. The VE examination items included the existence/absence of pharyngeal residue, laryngeal penetration, and aspiration of food and saliva. The patients were followed-up for 3months with individualized feeding therapy based on the results of the clinical/VE examination at baseline, and the incidence of pneumonia was examined as the primary outcome. In patients without pneumonia, the body weight change was also measured as a secondary outcome. The risk factors for pneumonia and body weight loss (of 3% or more) were identified among the clinical/VE examination items by a Cox proportional hazard analysis. Even with elaborative feeding therapy, 12 (8·1%) of the 148 patients developed pneumonia during the 3months follow-up period. The existence of signs of 'silent aspiration of saliva' or 'aspiration of saliva' detected by VE examination was a significant risk factor for both pneumonia and a body weight loss of 3% or more. This study shows that 'aspiration of saliva' detected by VE is a significant risk factor for both pneumonia and body weight loss in elderly patients living in nursing homes. © 2012 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2842.2011.02286.x

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

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

Embryonic stem cell-associated antigens are expressed in a variety of adult stem cells as well as embryonic stem cells. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 can be used to isolate dental pulp (DP) stem cells. DP cells showed plastic adherence, specific surface antigen expression, and multipotent differentiation potential, similar to mesenchymal stem cells (MSC). SSEA-4+ cells were found in cultured DP cells in vitro as well as in DP tissue in vivo. Flow cytometric analysis demonstrated that 45.5% of the DP cells were SSEA-4+. When the DP cells were cultured in the presence of all-trans-retinoic acid, marked downregulation of SSEA-3 and SSEA-4 and the upregulation of SSEA-1 were observed. SSEA-4+ DP cells showed a greater telomere length and a higher growth rate compared to ungated and SSEA-4- cells. A clonal assay demonstrated that 65.5% of the SSEA-4+ DP cells had osteogenic potential, and the SSEA-4+ clonal DP cells showed multilineage differentiation potential toward osteoblasts, chondrocytes, and neurons in vitro. In addition, the SSEA-4+ DP cells had the capacity to form ectopic bone in vivo. Thus, our results suggest that SSEA-4 is a specific cell surface antigen that can be used to identify DP stem cells.

DOI： 10.1016/j.yexcr.2012.01.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：1  

Resin coating materials have been used for composite resin or provisional restoration in order to prevent plaque accumulation on their surfaces. However, it is not clear whether the coating materials influence attachment of periodontal bacteria. Therefore, we investigated the effect of resin coating materials on the attachment of Porphyromonas gingivalis (Pg). The polymerized auto cure resin plates were coated with two resin coating materials. To estimate the Pg attachment, each plate was immersed in brain heart infusion medium containing Pg. The quantity of bacteria attached on each plate was evaluated by crystal violet quantification. Morphological change of Pg was recorded using scanning electron microscopy. Both coating groups presented significantly lower Pg attachment compared to the control. The Pg shapes on the plates with resin coating materials were similar to the non-treated control plates. The resin coating materials clearly prevent Pg attachment on the polymerized auto cure resin plate.

DOI： 10.4012/dmj.2011-164

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE SOC DENTAL MATERIALS DEVICES  

The purpose of this study was to evaluate if a low-shrinking composite can improve the bonding effectiveness of adhesives in highly constrained conditions. A low-shrinking composite ('els-extra low shrinkage', Saremco) was bonded in standardized occlusal Class-I cavities using a three-step ('cmf', Saremco) and a two-step etch-and-rinse adhesive ('XP Bond', Dentsply). Both adhesives were also combined with a conventional composite ('Z100', 3M ESPE). Half of the restored cavities were exposed to 20,000 thermo-cycles. 3-way ANOVA revealed a significant effect for the factors 'adhesive' and 'composite' (both p<0.0001), but not for 'thermo-cycling' (p=0.994). Significantly higher bond strengths were recorded for the low-shrinking composite than for the control composite, using either of the adhesives. The low-shrinking composite in combination with the three-step etch-and-rinse adhesive performed best in the high C-factor Class-I cavity. The two-step etch-and-rinse adhesive suffered strongly from polymerization-shrinkage stress, which could be partially restored by using the low-shrinking composite.

DOI： 10.4012/dmj.2011-261

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Recent studies have shown that infraorbital nerve constriction (IoNC)-induced mechanical allodynia has been attenuated by administration of highly purified 150-kDa Botulinum neurotoxin type A (BoNT/A). Here, we extend these studies to determine whether BoNT/A could attenuate IoNC-induced symptoms of thermal hyperalgesia. Instead of testing head withdrawal thresholds, a thermal operant assay was used to evaluate cortical processing of sensory input following IoNC. In this assay, a fasted rat's desire to obtain a food reward (sweetened condensed milk) is coupled to its ability to tolerate facial contact with a warm (45°C) thermode. Bilateral IoNC decreased the ratio of thermode contact duration/event, which is an indicative of thermal hyperalgesia. BoNT/A injection intradermally in the area of infraorbital nerve (IoN) innervation 7days after IoNC resulted in decreased number of facial contacts and increased the ratio of contact duration/event (measured at 14days after IoNC). The BoNT/A (2-200pg) effects were dose dependent and statistically significant at 100 and 200pg (P<0·05). Complete reversal of thermal hyperalgesia symptoms was obtained with a 200-pg dose, without affecting sham rat behaviour. Off-site (neck) injection of BoNT/A did not relieve thermal hyperalgesia, while co-injection of BoNT/A with a neutralising antibody in the area of IoN innervation prevented relief of thermal hyperalgesia. Neither IoNC nor BoNT/A injection affected operant assay parameters with a 24°C thermode, indicating selectivity of thermal hyperalgesia measurements. These results strongly suggest that intradermal injection of BoNT/A in the area of IoN innervation alleviates IoNC-induced thermal hyperalgesia in an operant assay. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1365-2842.2011.02236.x

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Other Link： http://orcid.org/0000-0002-4419-9643

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

Type A neurotoxin (NTX) of Clostridium botulinum was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at -30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons.

DOI： 10.1155/2012/648384

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Summary Occlusal dysesthesia refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. This systematic review aimed to draw a picture of such patients, to present an agreement of previously reported diagnostic criteria and to analyse the evidence level of the recommended management approaches. An electronic search for all relevant reports on occlusal dysesthesia was thoroughly performed based on previous nomenclatures (e.g. phantom bite, occlusal hyperawareness) in PubMed and The Cochrane Library in July, 2011. A total of 84 reports were matched, among which only 11 studies were included after a two-step (abstract and detailed full-text revision) screening process. Additionally, a thorough manual review of reference lists of the included reports enabled the inclusion of two additional studies. Data analysis revealed that 37 occlusal dysesthesia patients presented a mean age of 51・7 ± 10・6 years and were predominantly women (male/female: 1/5・1) with symptom duration of more than 6 years (average: 6・3 ± 7・5 years) and with concomitant psychological disturbances (e.g. mood disorders, somatoform disorders, personality disorders). Only four authors presented diagnostic criteria for occlusal dysesthesia, which served as the basis for an agreement in the diagnostic criteria. Treatment approaches included psychotherapy, cognitive/behaviour therapy, splint therapy and prescription of anti-depressants or anti-anxiety drugs. Classification of evidence level of management approaches, however, revealed that most of them were expert opinions with single- or multiple-case report(s). Future studies are necessary for a deeper understanding of the mechanisms behind the occlusal dysesthesia symptoms, and consequently, for improvements in evidence-based management approaches.

DOI： 10.1111/j.1365-2842.2012.02300.x

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The purposes of this study were to determine whether a response shift was observable after partial denture treatment and to identify the predictors that influenced the response shift magnitude and direction. A total of 173 consecutive patients with no more than eight missing teeth who received implant-supported, fixed or removable partial dentures at Okayama University Dental Hospital were asked to complete a full-version Oral Health-Related Quality of Life (OHRQoL) questionnaire before (pre-test) and after treatment (post-test). Additionally, a short form (then-test) consisting of seven questions selected from the full version had its reliability verified and was utilised to retrospectively assess the pre-treatment OHRQoL status. The difference between the summary scores of the then-test and the pre-test determined the response shift magnitude and direction. The then-test mean score (22・9 ± 6・6) was significantly lower (worse OHRQoL) than that of the pre-test (26・4 ± 5・2). The response shift effect size was of moderate magnitude and negative direction (d = -0・78). A multiple regression analysis showed that age (younger patients) (P &lt; 0・01), number of replaced teeth (fewer) (P &lt; 0・01) and pre-test scores (lower) (P &lt; 0・01) were the significant predictors for response shift. In conclusion, a response shift phenomenon with negative and moderate effect size was observed after partial denture treatment. The significant predictor variables were young age, fewer numbers of replaced teeth and lower pre-test scores.

DOI： 10.1111/j.1365-2842.2011.02241.x

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

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Language：English   Publisher：(一社)日本骨代謝学会  

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These results indicated painful disk displacement to possibly be correlated with ipsilateral muscle tenderness.

DOI： 10.1016/j.tripleo.2009.07.050

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：SPRINGER-VERLAG BERLIN  

CCN2/CTGF, previously known as Connective Tissue Growth Factor, is a crucial regulator of extra-cellular matrix (ECM), which promotes ECM synthesis and stabilization. As their family name clearly implies, matrix metalloproteases (MMPs) are also localized in the ECM, where they function as proteases, modulating cell signaling by cleaving proteins such as matrix proteins, growth factors and growth factor receptors. Strong expression of CCN2/CTGF in chondrocytic cells occurs through transcription enhancer dominant in chondrocytes (TRENDIC). Matrix metalloprotease-3 (MMP3) is a novel TRENDIC-binding transcription factor for CCN2/CTGF expression. First, MMP3 cDNA was cloned as a TRENDIC-binding factor by Southwestern screening. The interaction between MMP3 and TRENDIC was confirmed by a gel shift assay and chromatin immunoprecipitation. The CCN2/CTGF promoter was activated by transfected MMP3, whereas a TRENDIC mutant for the promoter lost the response. In addition, the knockdown of MMP3 suppressed CCN2/CTGF expression. Cytochemical and histochemical analyses demonstrated that MMP3 was detected in the nuclei of chondrocytic cells in culture and also in the nuclei of normal and osteoarthritic chondrocytes in vivo. The nuclear translocation of externally added recombinant MMP3 was observed in 30 min after the addition, and six putative nuclear localization signals were found in MMP3. These results indicated a novel trans-activation mechanism of CCN2/CTGF by the nuclear translocation of MMP3 through binding with TRENDIC in chondrocytes. Although MMPs historically had been recognized as a protease for extra-cellular proteins, this study indicated that it also stimulates ECM synthesis through CCN2/CTGF trans-activation. This novel regulatory role of the ECM may contribute to understanding the mechanism of not only the development, but also the pathogenesis of arthritis fibrosis and periodontitis.

DOI： 10.1007/978-90-481-3779-4_19

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Other Link： http://orcid.org/0000-0002-9600-4430

Language：Japanese   Publisher：日本歯科医学会  

顎関節症の治療に関しては現時点では充分なエビデンスが集積しているとは言い難く、診療に必要とされるガイドラインの作成や関連するエビデンス蓄積の必要性が高まっている。本プロジェクト研究は、1)現在顎関節症の治療に用いられているスタビライゼーション・スプリントのデザインならびに臨床介入術式についてのガイドラインを作成すること、2)補綴系顎関節症専門治療施設ならびに開業歯科医院を対象としてその治療実態に関する調査を行うこと、3)顎関節雑音に対するスタビライゼーション・スプリントの効果に関する文献的エビデンスを収集すること、の3点を目的とした。結果として、スタビライゼーション・スプリントのデザインならびに臨床介入術式についてはDelphi法変法を用いた合意形成を行い、介入手法ガイドライン(案)をまとめた。また、治療実態調査については、顎関節症外来14施設および開業歯科医院33施設を対象とした調査を行い、診療時間等に関する結果を得ることができた。また、スタビライゼーション・スプリントを用いた治療に関するエビデンス検索では、顎関節雑音の治療に有効であるとするエビデンスは現時点では得ることができなかった。(著者抄録)

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DOI： 10.11246/gakukansetsu.21.222

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2009&ichushi_jid=J02499&link_issn=&doc_id=20100108350003&doc_link_id=10.11246%2Fgakukansetsu.21.222&url=https%3A%2F%2Fdoi.org%2F10.11246%2Fgakukansetsu.21.222&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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Statin, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is known to promote bone formation. However, it is not clear whether statin affects the differentiation of pulp cells. This study used a cell proliferation assay, cell cycle analysis, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and in vivo transplantation to examine the effects of simvastatin on human dental pulp stem cells (DPSCs) in vitro and in vivo. Simvastatin at 1 mumol/L was able to significantly suppress the proliferation of DPSCs without inducing apoptosis. Quantitative RT-PCR revealed both osteocalcin and dentin sialophosphoprotein to be significantly up-regulated when DPSCs were cultured with simvastatin in comparison to bone morphogenetic protein-2 treatment. The in vivo transplantation data showed that simvastatin treatment promoted mineralized tissue formation. Taken together, these results suggest that statin might be an ideal active ingredient to accelerate the differentiation of DPSCs.

DOI： 10.1016/j.joen.2008.11.024

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DOI： 10.1016/j.neuroscience.2009.04.067

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Other Link： http://orcid.org/0000-0002-4419-9643

Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.toxicon.2008.04.019

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DOI： 10.11264/jjop.1.55

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Multiple roles have been already recognized for CCN2 in cartilage development and regeneration. However, the effects of CCN2 on bone regeneration remain to be elucidated. In this study, the utility of CCN2 on bone regeneration was examined in vitro and in vivo in combination with hydroxyapatite (HAp) as a scaffold. Human bone marrow stromal cells (hBMSCs) were isolated from human iliac bone marrow aspirates of healthy donors and expanded, and the effects of CCN2 on their proliferation and migration were examined in vitro. The proliferation of hBMSCs on a plastic or HAp plate was significantly enhanced by CCN2. Moreover, the migration of hBMSCs also dramatically increased by CCN2. Interestingly, a C-terminal signal modular fragment of CCN2 (CT-module) also enhanced the cell proliferation and migration as efficiently as the full-length CCN2. Next, in order to estimate the effect of CCN2 on the migration and survival of hBMSCs and bone formation inside the HAp scaffold in vivo, two experiments were performed. First, the porous HAp carrier was cultured with hBMSCs for a week, and the cell-scaffold hybrid was transplanted with or without CCN2 subcutaneously into immunocompromised mice. CCN2 accelerated the hBMSC-like cell migration and survival inside the porous HAp within 4 weeks after transplantation. Second, the porous HAp carrier with or without CCN2 was directly implanted into bone defects within a rabbit mandible, and bone regeneration inside was evaluated. As a result, CCN2 efficiently induced the cell invasion and bone formation inside the porous HAp scaffold. These findings suggest that CCN2 and its CT-module fragment could be useful for regeneration and reconstruction of large-scale bone defects.

DOI： 10.3727/000000008783907143

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Language：Japanese   Publisher：岡山歯学会  

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

OBJECTIVES: Titanium has in recent years become a material of great opportunities in dentistry and orthopedics. In this study, we searched for a method to effectively pre-treat titanium as part of an adhesive luting and/or resin-veneering procedure. METHODS: Ti plates were treated with two different solutions of hydrochloric acid (0.1, 1N), 37wt% phosphoric acid or kept untreated (control). The tensile bond strength of the composite cement (Panavia Fluoro Cement, Kuraray) to the untreated and pre-treated Ti plates was determined without and after 20,000 thermo-cycles. XPS was used to chemically analyze the effect of the three Ti pre-treatments, as well as the interaction of 10-methacryloxydecyl dihydrogen phosphate (10-MDP; functional monomer of Panavia Fluoro Cement) with Ti treated with 1N HCl. RESULTS: Although no significant difference in immediate tensile bond strength was measured, thermo-cycling significantly decreased the bond strength of all experimental groups except for Ti treated with 1N HCl. No difference in surface roughness was found between untreated and treated Ti. XPS demonstrated that HCl effectively decontaminated Ti in a dose-dependent manner, while H(3)PO(4) was strongly adsorbed on the Ti surface. While the latter potentially inhibits adsorption of the phosphoric groups of the functional monomer 10-MDP, Ti pre-treated with 1N HCl improved the adsorption of 10-MDP as compared to untreated Ti. SIGNIFICANCE: It is concluded that 1N HCl effectively pre-treats Ti in order to make it more receptive to resin, while H(3)PO(4) should better not be used.

DOI： 10.1016/j.dental.2005.08.002

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Language：Japanese   Publisher：(公社)日本口腔インプラント学会  

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PATIENT: The patient was a 56-year-old female, suffering from severe burning pain in the left maxillary alveolar area. The pain was initiated by periodontal curettage under no local anesthesia. No abnormal local findings in dental X-ray images and no abnormal central nervous system findings in brain magnetic resonance images were observed. Extraction of the tooth temporarily abated her pain, however the pain recurred gradually. Since the observed signs and symptoms of the patient agreed well with the diagnostic standard for continuous neuropathic pain (atypical alveolar pain) of Graff-Radford & Solberg (1992), medications (tricyclic antidepressant, non-steroidal anti-inflammatory drug (NSAID), anxiolytics, topical application of capsacin cream) and supportive psychological therapy have been administered continuously. To measure symptom severity over a long term, daily amounts of taken NSAID and anxiolytics were recorded continuously by the patient in a simple table diary for 7 years. As a result, the total amount of the drugs per month gradually decreased with the passage of time. DISCUSSION AND CONCLUSIONS: Clinical evidence regarding the prognosis of continuous neuropathic pain in the orofacial region is obviously insufficient, making it difficult to inform such patients of their prognosis of the disorder on the basis of clinical evidence. In this report, we have plotted the total amount of drugs taken per month by the patient as a good reference for the pain severity and the results clearly suggest that pain severity decreased with time. This kind of information may help both clinicians and patients for case-based explanation of the disorder.

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The aim of this study was to evaluate the effect of pre-treatment of titanium (Ti) surface with polyphosphoric acid on the initial attachment of human bone marrow derived mesenchymal stem cells (hBMSCs). The results of this study revealed that adsorption of polyphosphoric acid to Ti significantly enhanced initial attachment of hBMSCs. © 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.ics.2005.06.091

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

Appropriate dental implants are known to improve the quality of life in totally and partially edentulous patients, as well as to prevent future tooth loss, and so prosthetic treatment modalities have drastically changed recently with reconstruction therapy. However, dental implant therapy did not win the confidence of the dental community in the early developmental stage, until osseointegration between titanium and surrounding bone tissue was discovered and the modality utilizing osseointegration became reliable and produced durable treatment outcomes for long-term function. On the other hand, the biological mechanism of osseointegration has not been clarified yet and the time required for osseointegration is still long, e.g. three to four months. As well, when the implant is applied in the upper posterior region, the acquisition of osseointegration and the long-term survival of the implant are still not clinically adequate. Therefore, to reduce the time required for osseointegration and to regenerate enough alveolar bone mass in the target implantation site, the oral implant modality must be made more useful and potent as one of the treatment options for partial and total edentulism. With this background, we have studied biological strategies for reducing the time required for osseointegration and for regenerating enough alveolar bone mass, e.g., investigation of the specific genes for osseointegration between titanium and bone, nano-level surface modification of the titanium, biodegradable apatite foam for alveolar bone regeneration, application of bone formation-related growth factors with biological scaffold, and autologous cell transplantation of bone marrow derived mesenchymal stem cells. In this article, we review the current status of regenerative medicine being applied in prosthodontics and discuss our future research direction.

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Language：Japanese   Publisher：(公社)日本矯正歯科学会  

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

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UNLABELLED: CTGF/CCN2, a hypertrophic chondrocyte-specific gene product, possessed the ability to repair damaged articular cartilage in two animal models, which were experimental osteoarthritis and full-thickness defects of articular cartilage. These findings suggest that CTGF/CCN2 may be useful in regeneration of articular cartilage. INTRODUCTION: Connective tissue growth factor (CTGF)/CCN2 is a unique growth factor that stimulates the proliferation and differentiation, but not hypertrophy, of articular chondrocytes in vitro. The objective of this study was to investigate the therapeutic use of CTGF/CCN2. MATERIALS AND METHODS: The effects of recombinant CTGF/CCN2 (rCTGF/CCN2) on repair of damaged cartilage were evaluated by using both the monoiodoacetic acid (MIA)-induced experimental rat osteoarthritis (OA) model and full-thickness defects of rat articular cartilage in vivo. RESULTS: In the MIA-induced OA model, quantitative real-time RT-PCR assays showed a significant increase in the level of CTGF/CCN2 mRNA, and immunohistochemical analysis and in situ hybridization revealed that the clustered chondrocytes, in which clustering indicates an attempt to repair the damaged cartilage, produced CTGF/CCN2. Therefore, CTGF/CCN2 was suspected to play critical roles in cartilage repair. In fact, a single injection of rCTGF/CCN2 incorporated in gelatin hydrogel (rCTGF/CCN2-hydrogel) into the joint cavity of MIA-induced OA model rats repaired their articular cartilage to the extent that it became histologically similar to normal articular cartilage. Next, to examine the effect of rCTGF/CCN2 on the repair of articular cartilage, we created defects (2 mm in diameter) on the surface of articular cartilage in situ and implanted rCTGF/CCN2-hydrogel or PBS-hydrogel therein with collagen sponge. In the group implanted with rCTGF/CCN2-hydrogel collagen, new cartilage filled the defect 4 weeks postoperatively. In contrast, only soft tissue repair occurred when the PBS-hydrogel collagen was implanted. Consistent with these in vivo effects, rCTGF/CCN2 enhanced type II collagen and aggrecan mRNA expression in mouse bone marrow-derived stromal cells and induced chondrogenesis in vitro. CONCLUSION: These findings suggest the utility of CTGF/CCN2 in the regeneration of articular cartilage.

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Articular cartilage is always subjected to various types, magnitudes and cycles of mechanical stress. While it has been recognized that these stresses regulate the chondrocyte growth and differentiation, the mechanism is still unclear. Here, we summarize the effect of mechanical stress on cartilage metabolism from the point of view of development, growth, pathology and therapeutic aspect.

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Language：Japanese   Publisher：岡山歯学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

OBJECTIVE: To understand bone regeneration process after tooth extraction could be a clue to develop a new strategy for alveolar bone reconstruction. Recently, accumulated evidences support that connective tissue growth factor (CTGF) is implicated in tissue repair of many tissues. In this study, we investigated the spatial and temporal expression of CTGF in the rat tooth extraction sockets. DESIGN: Five weeks old wild type male rats (weighing 120 g) were used for this experiment. Expression of CTGF was determined by immunohistochemistry and in situ hybridization in the rat upper molar tooth extraction sockets at 2, 4, 7, 10 and 14 days after tooth extraction. RESULTS: CTGF was expressed strongly in the endothelial cells migrating into the granulation tissue at the bottom of the sockets during 4 days after tooth extraction. During the reparative process, no apparent chondrocyte-like cell appeared in the sockets, while osteoblast-like cells proliferated in the sockets with low CTGF expression at 7, 10, 14 days after extraction. As expected, no staining was observed with the preimmune rabbit IgG and CTGF sense probe. CTGF may play an important role in angiogenesis and granulation tissue formation specifically at early healing stage after tooth extraction to initiate alveolar bone repair. CONCLUSION: CTGF was expressed at early healing stage of the rat tooth extraction wound.

DOI： 10.1016/S0003-9969(03)00153-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Intern. and American Associations for Dental Research  

Although excessive mechanical stress is assumed to be one of the factors contributing to pathogenesis of temporomandibular joint (TMJ) osteoarthritis (OA), no pure mechanical-stress-induced OA model has been developed without surgical manipulation or puncture of the joint cavity. The purpose of this study was to establish a genuine mechanical-stress-induced OA model of the rabbit TMJ. In the experimental rabbits, repetitive, forced jaw-opening, 3 hrs/day for 5 days, was applied with the use of a general anesthesia protocol. By histological assessment of the TMJ articular tissues, partial eburnation of the articular cartilage, reactive marginal proliferation of the articular cartilage chondrocytes, and nested proliferation of chondrocytes in the subchondral bone area were observed at 7 days after the repetitive, forced-jaw-opening period. These results suggest that the repetitive, forced-jaw-opening protocol without surgical intervention can induce evident OA-like lesions in the rabbit TMJ, and this OA model may greatly contribute to the elucidation of the cartilage degradation mechanism in TMJ OA.

DOI： 10.1177/154405910308200914

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

42歳男.強度のいびきと無呼吸を家族に指摘された.終夜睡眠ポリグラフィーでは無呼吸指数が33.4,無呼吸低呼吸指数が48.5で,重度の睡眠時無呼吸症と診断した.経鼻的持続陽圧呼吸療法は不快感から施行できず,口腔アプライアンス療法として,上顎と下顎に装着した全歯被覆型のアプライアンスを自作のハーベストタイプの金属製連結装置で連結し,下顎を相対的に前方位で保持させるツーピース型を使用した.治療開始時の下顎前方誘導量は,最大前方滑走量の50%程度の前突量,即ち切端咬合位からスタートし,1ヵ月に1度の頻度で連結装置に金属製のスペーサを追加して前方誘導量を増加させた.その結果,7ヵ月後には無呼吸指数4.5,無呼吸低呼吸指数9.7と著しく改善し,徐波睡眠も全睡眠時間の1.5%から17.4%に増加した.最終的な下顎前方誘導量は最大滑走量の70%であった

DOI： 10.2186/jjps.46.649

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J01189&link_issn=&doc_id=20030116360005&doc_link_id=%2Fdv5hotet%2F2002%2F004605%2F005%2F0649-0654%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdv5hotet%2F2002%2F004605%2F005%2F0649-0654%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(公社)日本補綴歯科学会  

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The purpose of this study was to compare and contrast blood volume changes transcutaneously measured using near-infrared (NIR) spectroscopy against water signal intensity changes taken from a transverse T2-weighted MR image of the masseter muscle in healthy human subjects before, during and after contraction. Eight healthy non-smoking males with no history of chronic muscle pain or vascular headaches participated (mean age: 23.9 ± 0.6 years). The MRI data were gathered using a turbo spin echo sequence (TR: 2300 ms; TE: 90 ms; FOV: 188 × 300 mm; scanning time: 30 s; slice thickness: 10 mm) and the slice level was set at the mid-point between the origin and insertion of the masseter. Intramuscular haemoglobin (Hb) levels and water content of the right masseter muscle were continuously monitored for 2 min before, 30 s during and 15 min after a maximum voluntary clenching (MVC) task. Both the near-infrared and MRI data were baseline-corrected and normalized and mean levels were established and plotted. Plots of the data showed that both near-infrared-based total Hb and T2-weighted MRI-based signal-intensity levels clearly decreased during contraction and a clear post-contraction rebound response was evident after the contraction. The near-infrared data were found to be highly correlated with MRI-based signal-intensity data (Pearson&#039;s r = 0.909, P &lt; 0.0001). In conclusion, these data provide powerful evidence that near-infrared data (total Hb), transcutaneously taken from the masseter muscle in humans, will reflect the intramuscular water signal intensity changes seen using a T2-weighted MRI imaging method. © 2001 Elsevier Science Ltd.

DOI： 10.1016/S0003-9969(01)00030-9

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

A three-dimensional, static mathematical calculation of the stomatognathic system was done to predict total temporomandibular joint (TMJ) loading at different levels of jaw opening. The model assumed that muscle forces acting on the mandible could be simulated by a combination of contractile components (CCs) and elastic components (ECs) and that static equilibrium existed within the body of the mandible. The model also imposed the constraint that any generated joint reaction force would act on the centre of the condyle. The results of the model demonstrated that under all conditions of opening and for all values of the elastic modulus selected, the forces between the TMJ condyle and the articular eminence were compressive in nature. The compressive force magnitude increased from 2 .7 to 27 .6 N incrementally as the jaw opened from 10 to 40 mm. Overall data in this study indicated that the TMJ tissues undergo low levels of compression at open positions up to 40mm. Finally, the condition of trismus (increased jaw closing activation with opening) was simulated, the Joint reaction force at 20 mm opening increased from 7 .7 to 64 .9 N with only a 20% activation of the dosers.

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Aims: To investigate the natural course of symptoms of temporomandibular disorders (TMD) in a non-patient population and to estimate the strength of the relationship between several hypothesized risk factors and precipitation and perpetuation of the symptoms. Methods: A total of 672 randomly selected citizens of Okayama City was requested to answer the same self-administered questionnaire that they had answered 4 years earlier. The mailed questionnaire failed to reach 58 subjects at the second survey, and 367 of the remaining subjects (59.8%) responded. The fluctuation of TMD symptoms was assessed by comparison of 6 pairs of answers for questions regarding temporomandibular joint (TMJ) pain, limitation of mouth opening, TMJ noise, headache, neck pain, and shoulder stiffness. Six factors (age under 40, female, clenching habit, history of extrinsic trauma, sleep disturbance, and family history of TMD) were tested for their relative risk in precipitating and perpetuating each TMD symptom by the use of its confidence interval to define significance. Results: The incidence of TMD symptoms ranged from 6.1% (TMJ pain) to 12.9% (TMJ noise). More than half of the subjects who had reported TMJ and neck pain at the initial survey no longer reported these symptoms at the second survey, whereas TMJ noise and shoulder stiffness remained in more than 70% of the subjects. Individuals under 40 years old had a 3.3:1 increased risk of precipitating TMJ noise (P &lt
0.01), individuals with a history of extrinsic trauma had a 2.85:1 increased risk of precipitating limited mouth opening (P &lt
0.01), and females had a 2.81:1 increased risk of perpetuating TMJ pain (P &lt
0.01). Conclusion: The possible etiologic significance of these factors in TMD should be validated hv future research.

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The aim was to compare haemodynamic responses in trapezius muscles to cold pressor stimulation in individuals with localized trapezius myalgia and asymptomatic controls. Nine males with chronic localized pain in the trapezius (mean age, 23.2 years) and nine male controls (mean age, 24.6 years) who had no medical history of migraine, hypertension or sustained pain in the trapezius region were investigated. Two experimental (cold pressor and mock) trials were performed in a randomly assigned sequence. In the cold pressor trial the participant's left foot and ankle were immersed in 4°C cold water for 2 min
the mock trial was done without that stimulus. Blood volume was continuously recorded 1 min before, 2 min during, and 5 min after cold pressor stimulation using near-infrared spectroscopy. Each participant's blood-volume data were baseline-corrected and submitted to statistical analysis. Results showed that the individuals with muscle pain exhibited a significantly lower mean blood volume than the controls during cold pressor stimulation (p = 0.0367). Upon withdrawal of that stimulation, the mean blood volume in both groups fell below the baseline. These results suggest that individuals with chronic regional trapezius myalgia have less capacity to vasodilate this muscle during cold pressor stimulation than those without such myalgia. It is not yet known if this difference in the haemodynamic response is a cause or an effect of the myalgia.

DOI： 10.1016/S0003-9969(99)00082-5

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Adenovirus vector system is expected to be useful for direct gene therapy for joint disease. This study first sought to confirm that foreign genes can be transferred to articular chondrocytes in primary culture. Next, recombinant adenovirus vectors harbouring β-galactosidase gene (LacZ) was injected directly into the temporomandibular joints of Hartley guinea-pigs to clarify the in vivo transfer availability of the adenovirus vectors. Specifically, recombinant adenovirus harbouring LacZ gene (Ax1CALacZ) was injected into the upper joint cavities of both mandibular joints of four male 6-week-old Hartley guinea-pigs. Either the same amount of recombinant adenovirus without LacZ gene (Ax1w) suspension (placebo) or the same amount of phosphate-buffered saline solution (control) were injected into the upper joint cavities of both joints of another four male guinea-pigs. At 1, 2, 3 and 4 weeks after injection, the joints were dissected and the expression of delivered LacZ was examined by 5-bromo-4-chloro-3-indolyl-β-D- galactopyranoside (X-gal) staining and reverse transcriptase-polymerase chain reaction (RT-PCR). To investigate the expression of transferred gene in other organs, total RNA was extracted from liver, kidney, heart and brain and the expression of Latz mRNA and 18 S ribosomal RNA were analysed by RT-PCR. Clear expression of LacZ was observed in the articular surfaces of the temporal tubercle, articular disc and synovium of the temporomandibular joints even 4 weeks after injection in the Ax1CALacZ-injected group, while no expression was detected in placebo and control groups. Histological examination confirmed that LacZ activity was clearly detected in a few cell layers of the articular surface tissues, which is much more efficient than in a previously study of the knee joint. In the other organs, expression of the delivered transgene was not observed. Based on these findings, direct gene delivery into the articular surface of the temporomandibular joint using the adenovirus vector is feasible as an effective in vivo method.

DOI： 10.1016/S0003-9969(99)00069-2

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Eight healthy non-smoking males (mean age: 24.1 ± 1.1 years) without any history of chronic muscle pain and migraine participated in this study. Haemoglobin (Hb) and oxygen (O2) saturation in the right masseter muscle were continuously recorded with a non-invasive near-infrared spectroscopic device. Heart rate and blood pressure were also recorded. The experiment had three phases: a placebo drug (physiological saline) with cold-pressor trial, a 30-sec maximal voluntary clenching (MVC) trial, and a propranolol with cold-pressor trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the cold-pressor stimulation (4°C). Physiological saline (20 ml) or propranolol hydrochloride (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 20 min before the baseline recording and participants did not know which solution (saline or propranolol) was being infused. For the MVC trial, each participant was asked to perform a 30-sec clench of their jaw-closing muscles. There was a rest period of 15 min between each trial. The individual Hb and O2 data were normalized so that the baseline at the beginning of the experiment was equal to zero, and the Hb and O2 data were normalized as a percentage of the individual's own highest absolute Hb and O2 after and during the MVC, respectively. The results showed that the mean baseline Hb 1 min before cold-pressor stimulation was significantly lower in the β- blocker trial than in the placebo trial (p=0.035). The mean change in Hb from baseline during cold-pressor stimulation in the β-blocker trial was also significantly less than in the placebo trial (p = 0.035). The mean Hb rebound change after the cold-pressor stimulation in the β-blocker trial was significantly higher than in the placebo trial, and no significant heart- rate differences were observed in the period after cold-pressor stimulation. Overall, the mean heart rate before and during that stimulation was significantly lower in the β-blocker trial than the placebo trial (p &lt
0.001). There was no significant mean blood-pressure difference between placebo and β-blocker trials at any time. These results suggest that β- adrenoceptor blocking decreases the blood volume in the resting masseter, suppresses the incremental blood-volume change during cold-pressor stimulation, and discloses a hidden vasoconstrictive effect after that stimulation.

DOI： 10.1016/S0003-9969(99)00028-X

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Language：Japanese   Publisher：(公社)日本補綴歯科学会  

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Language：English   Publisher：(公社)日本生化学会  

機械的刺激による軟骨の分解について調べた.Flexercell strain unitを用いて周期的張力(CTF)を培養軟骨細胞に加えたところ,5kPa及び15kPaの高頻度CTFにより,DNA合成,プロテオグリカン合成,コラーゲン合成の低下が見られた.15kPaの高頻度CTFではIL-1,matrix metalloproteinase-2(MMP-2),MMP-9のmRNAの発現と活性型MMP-9の産生が増加した.この時,プロテオグリカンの分解が促進したが,MMPの阻害剤の存在下では分解の促進が抑えられた.張力を小さくすると,軟骨の分解に関わる遺伝子の発現誘導は見られなかった.強度の高頻度CTFはIL-1,MMP-2,MMP-9のmRNAの発現,及び活性型MMP-9の産生を増大させることから,周期的な機械的ストレスが軟骨の分解を引き起こすと考えられる

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=1999&ichushi_jid=J04549&link_issn=&doc_id=19990603080012&doc_link_id=10005463964&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F10005463964&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Publishing type：Research paper (scientific journal)  

To find specific humoral antibodies in sera from patients with temporomandibular joint (TMJ) osteoarthritis (OA), an immortal human chondrocyte (HCS-2/8) and osteoblast (Saos-2) cell line derived from a chondrosarcoma and an osteosarcoma, respectively, were used as source proteins of human antigens. Patients with chronically painful TMJ OA (n = 18) but no other joints symptoms were selected from a consecutive series of patients with temperomandibular disorders and sex-matched asymptomatic controls (n = 8) were also recruited. Cellular proteins of the HCS-2/8 and Saos-2 cells were subjected to Western blotting with the OA and control sera as probes. Band-recognition frequency and the peak optical density of the band were compared between groups by χ2 and t-tests. OA sera recognized various bands for the chondrocytes, and one of these (47-kDa) was specific for the OA sera. In two OA patients whose treatment outcome was less favorable, the reactivity against the 47-kDa protein was relatively high. In addition, the OA sera clearly cross-reacted with recombinant HSP47. Based on these findings, an autoimmune reaction against chondrocytes could be one of the exaggerating and/or perpetuating mechanisms in the pathophysiology of osteoarthritic TMJs, and the humoral antibody titre against the HSP47-like protein derived from the chondrocytes could be one of the possible markers for the prognosis of the joint pathology.

DOI： 10.1016/S0003-9969(99)00009-6

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This study evaluated the effect of intravenous infusion of a non- selective α-adrenergic blocking agent on masseter muscle haemodynamics induced by 4°C cold pressor stimulation (CPS) of the right foot and ankle, which reportedly evokes a rapidly increasing sympathetic nerve activity in human skeletal muscle. Nine healthy non-smoking males (mean age 23.7±2.1 year) with no history of chronic muscle pain or migraine participated. The haemoglobin (Hb) concentration in the right masseter was continuously recorded by non-invasive, near-infrared spectroscopy. Heart rate and blood pressure were also recorded. The experiment involved the following sequence: (1) a placebo (physiological saline) with a CPS trial
(2) a 30-sec maximal voluntary clenching (MVC)-only trial
and (3) an α-adrenergic blocking agent with a CPS trial. The saline and drug trials each involved continuous recording for 1 min before, 2 min during and 5 min after the CPS. Physiological saline (20 ml) or phentolamine mesylate (20 ml) were infused at the rate of 2 ml/min. This infusion was begun 15 min before baseline recording and participants were not aware which solution (saline or phentolamine) was being infused. For the MVC trial, each participant performed a 30-sec MVC of his jaw-closing muscles followed by a 15-min rest between, each trial. The individual Hb data were adjusted so that the baseline at the beginning of the experiment was equal to zero and all data were normalized as a percentage of the individual's highest absolute Hb change seen after the MVC. The mean baseline Hb concentrations 1 min before CPS were significantly higher in the α-blocker trial (83.6%) than in the placebo saline trial (P &lt
0.001). The change in mean Hb concentration from baseline during CPS in the α-blocker trial was significantly less than in the placebo trial (P = 0.006). Mean heart rate before CPS was also significantly higher in the α-blocker trial (85.2 beats/min) than in the placebo trial (69.6 beats/min) (P &lt
0.001). There were no significant differences in the mean systolic and diastolic blood pressures between the placebo and α-blocker trials in any time period. The results suggest that non-selective α-adrenoceptor blockade increases the blood volume in the masseter muscle. This change might be due to a combination of peripheral vasodilation and an increase in cardiac output.

DOI： 10.1016/S0003-9969(98)00127-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Biochemical Society  

Connective tissue growth factor (CTGF) is a novel cysteine-rich, secreted protein. Recently, we found that inhibition of the endogenous expression of CTGF by its antisense oligonucleotide and antisense RNA suppresses the proliferation and migration of vascular endothelial cells. In the present study, the following observations demonstrated the angiogenic function of CTGF in vitro and in vivo: (i) purified recombinant CTGF (rCTGF) promoted the adhesion, proliferation and migration of vascular endothelial cells in a dose-dependent manner under serum-free conditions, and these effects were inhibited by anti-CTGF antibodies
(ii) rCTGF markedly induced the tube formation of vascular endothelial cells, and this effect was stronger than that of basic fibroblast growth factor or vascular endothelial growth factor
(iii) application of rCTGF to the chicken chorioallantoic membrane resulted in a gross angiogenic response, and this effect was also inhibited by anti-CTGF antibodies. (iv) rCTGF injected with collagen gel into the backs of mice induced strong angiogenesis in vivo. These findings indicate that CTGF is a novel, potent angiogenesis factor which functions in multi-stages in this process.

DOI： 10.1093/oxfordjournals.jbchem.a022414

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Biochemical Society  

To clarify the mechanism of cartilage degradation induced by mechanical stress, we investigated the influence of cyclic tension force (CTF) on the metabolism of cultured chondrocytes. The chondrocytes were exposed to CTF using a Flexercell strain unit. Five or 15 kPa of high frequency CTF significantly inhibited the syntheses of DNA, proteoglycan, collagen, and protein. Fifteen kPa of high frequency CTF induced the expression of interleukin-1 (IL-1), matrix metalloproteinase (MMP)-2 and -9 mRNA, and increased the production of pro- and active-MMP-9. The degradation of proteoglycan was inhibited by and MMP inhibitor, indicating that MMPs are involved in the degradation of proteoglycans induced by high frequency CTF. Moreover, reducing the frequency of CTF from high to low decreased the inhibition of proteoglycan synthesis. These findings suggest that the CTF frequency is one of the key determinants of chondrocyte metabolism. Low magnitude CTF, whether high or low frequency, did not cause the gene expression of cartilage degradation factors, suggesting that this CTF magnitude causes only minor changes in the cartilage matrix. High magnitude and frequency CTF caused the gene expression of IL-1 and MMP-9, followed by increases in the production of MMP-2 and -9 proteins, suggesting that excessive and continuous cyclic mechanical stress induces the production of IL-1 and MMP-9, resulting in cartilage degradation.

DOI： 10.1093/oxfordjournals.jbchem.a022376

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

Objective: To determine the effect of sustained incisai clenching on the width of the temporomandibular joint space. Methods: Nine normal subjects clenched on an anterior appliance for 10 min at 49 N. Sagittal tomograms were obtained during comfortable closure in the intercuspal position (ICP) (ICP- Before), comfortable closure on bite force transducer without clenching (BFT-Before), start of clenching (BFT-0), end of 5 min clenching (BFT-5), end of 10 min clenching (BFT-10), comfortable closure on the bite force transducer immediately after clenching (BFT-After) and comfortable closure in ICP after clenching (ICP-After). Joint space dimensions were automatically measured by a computerized image analysis system. Results: The minimum joint space dimension was significantly reduced at BFT-5 (P = 0.0381), BFT-10 (P = 0.0019) and BFT-After (P = 0.0053) in relation to BFT-Before. The condylar position was also significantly shifted upward at BFT-0 (P = 0.0422), BFT-5 (P = 0.0005), BFT- 10 (P = 0.0001), and BFT-After (P = 0.0004) in relation to BFT-Before. Conclusion: Sustained incisai clenching at 49 N causes significant anterior joint space reduction. We believe this is due to marked compression of the articular cartilage and disc.

DOI： 10.1038/sj.dmfr.4600443

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

Aims: Stabilization appliances and mandibular anterior repositioning appliances have been used to treat patients with internal derangement of the temporomandibular joint (TMJ) based on the assumption that these appliances work by decompressing the TMJ. The purpose of this study was to indirectly test this assumption. Methods: Bilateral TMJ tomograms of 7 subjects with unilateral anterior disc displacement without reduction (ADDwor) were taken during comfortable closure and during maximum clenching in maximum intercuspation
tomograms were also taken with the 2 types of occlusal appliances in use. Outlines of the condyle and the temporal fossa were automatically determined by an edgedetection protocol, and the minimum joint space dimension of the joints with and without ADDwor was automatically measured for each experimental condition as the outcome variable. Results: Upon comfortable closure and maximum clenching, the minimum joint space dimensions of the ipsilateral and contralateral joints with the use of stabilization appliances and mandibular anterior repositioning appliances were not significantly different from those seen in maximum intercuspation. Conclusion: These findings do not indicate that these appliances induce an increase in joint space during closing and clenching in joints with ADDwor.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Intern. and American Associations for Dental Research  

Single items from a typical clinical examination have proved disappointing in their predictive value for temporomandibular joint (TMJ) disc displacement. Only one criterion (the 12 o'clock) is used to diagnose normal disc position. According to this criterion, the posterior band of the disc should be located at the top of the condyle, at the 12 o'clock position. The purpose of this study was to determine which signs and symptoms provide a valid prediction of the condition of the joint based on 4 magnetic resonance imaging (MRI) criteria used to define normal disc position. Sagittal MRI and clinical findings of 137 temporomandibular disorder patients and 23 normal asymptomatic volunteers were used. Three calibrated and blinded observers interpreted the images. Disc position with the mouth closed was evaluated based on 4 MRI criteria: 12, 11, 10 o'clock, and the intermediate zone. Disc position with the mouth open was determined based on one criterion. It was considered normal if the intermediate zone of the disc was located between the condyle and the articular eminence. Joints were classified as normal or as having disc displacement with or without reduction. The sensitivity and specificity of multiple clinical parameters for predicting the condition of the joint established by each of these 4 gold-standard MRI criteria were then determined. Regarding disc displacement with reduction, significant differences were observed in the sensitivity and specificity of all of the clinical parameters used to predict the imaging diagnosis established by each of the criteria. Concerning disc displacement without reduction, no significant differences were observed. The intermediate zone criterion was the criterion that most accurately reflected the condition of the joint. The clinical predictability of the disorder diagnosed according to this criterion suggests that clinical findings alone are too often nonspecific as predictors of the imaging stage of disc displacement. However, we found that combining the most sensitive clinical items to predict the disorder and using an overall criterion for positivity to interpret the results led to an impressive increase in the specificity of the combination, enabling false-positive diagnoses to be excluded.

DOI： 10.1177/00220345990780020401

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Cold pressor stimulation reportedly increases sympathetic nerve activity in human skeletal muscles. This study examined the effect of cold pressor stimulation on the resting haemodynamics of the right masseter muscle in normal individuals, using near-infrared spectroscopy. Nine healthy non- smoking males with no history of chronic muscle pain or vascular headaches participated. Their right hand was immersed in a water bath (4, 10, 15°C) for exactly 1 min. Each trial lasted 7 min (1 min before, 1 min during, 5 min after stimulation) and a strictly random order was utilized for the three test temperatures and the mock trial. Masseter muscle haemoglobin concentration and oxygen saturation, as well as heart rate and blood pressure, were continuously recorded in each trial. After completing the four trials, each participant produced and sustained a 30-s maximum voluntary clench in the intercuspal position. Data across the four trials were baseline-corrected and then magnitude-normalized to the individual's highest absolute haemoglobin and oxygen signal during the 30-s maximal clenching effort. Haemoglobin and oxygen saturation increased progressively during cold pressor stimulation as the water temperature decreased (Hb, p &lt
0.0001
O2, p = 0.0327)
very little effect was seen during the mock trial. Heart rate and blood pressure also increased progressively during the stimulation as the temperature decreased (heart rate, p = 0.0013
systolic blood pressure, p = 0.0042
diastolic blood pressure, p = 0.0156). These data suggest that cold pressor stimulation induces a strong increase in intramuscular blood volume which appears to be due to both a local vasodilative response and increased cardiac output.

DOI： 10.1016/S0003-9969(98)00072-7

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The purpose of this study was to investigate the relationship between osseous changes in the temporomandibular joint (TMJ) and dental attrition in the Japanese macaque. One hundred and thirty Japanese macaque skulls (54 male and 76 female) from animals which had been bred in the same environment, were randomly sampled from a collection at the Primate Research Institute of Kyoto University. The age at death had been recorded in all cases. TMJ osseous changes were independently evaluated by three examiners, and were defined as an irregular surface or a perforated compact bone layer with a markedly irregular surface on either the temporal or condylar components. Age was a significant factor in predicting TMJ osseous changes (P &lt; 0.001). A strong relation was observed between age and dental attrition (P &lt; 0.001), while dental attrition was not a significant factor in predicting TMJ osseous changes (P = 0.334). The prevalence TMJ osseous changes in male animals was slightly higher than in females (P = 0.057). The results of this study suggest that osseous changes in the macaque TMJ are mainly related to age, not to dental attrition.

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

The relationship between signs and symptoms of temporomandibular disorders (TMD) and bilateral occlusal contact patterns was investigated in 143 TMD patients (mean age: 34.0 ± 15.9 years
38 male and 105 female). In addition to an interview regarding chief complaints and accompanying symptoms, various muscles and the temporomandibular joints were palpated bilaterally and occlusal analyses were made. Only 5 out of 108 paired variables were found to be significantly associated by using the chi-squared test. Medial pterygoid muscle pain on palpation showed significant associations with the occlusal contact pattern (P &lt
0.005), especially working side contacts (interocclusal tooth contacts on the working side) (P &lt
0.005), during contralateral excursions
sternocleidomastoid muscle pain on palpation showed a significant association with balancing side contacts (interocclusal tooth contacts on the balancing side) during ipsilateral excursions P &lt
0.05)
shoulder stiffness and pain in the eye showed significant associations with balancing side contacts during contralateral excursions (P &lt
0.05). The results show only a weak relationship between some TMD symptomatology and bilateral occlusal contact patterns during lateral excursions. The findings suggesting the specific laterality of a few TMD signs and symptoms associated with particular occlusal contacts may deserve closer case-control study. © 1998 Blackwell Science Ltd.

DOI： 10.1046/j.1365-2842.1998.00262.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Objective. This study was undertaken to evaluate different criteria to establish normal disk position on magnetic resonance images. Study design. Magnetic resonance image findings of 137 consecutive patients with temporomandibular disorders and 23 asymptomatic volunteers were used in this study. Three calibrated observers interpreted the images individually. Four closed-mouth and 1 open-mouth criteria were tested for their ability to define normal and abnormal temporomandibular joint disk positions on magnetic resonance images. Results. For the 46 joints in the asymptomatic volunteers, the criterion that yielded the highest percentage of normal disk position diagnoses was the disk's intermediate zone (93.5%). Clock face criteria produced the following declining percentages of normal disk position diagnoses: 10 o'clock, 82.6%
11 o'clock, 63.0%
and 12 o'clock, 39.1%. Similar results were obtained for the patients with temporomandibular disorders. In both groups, as the number of normal disk position diagnoses declined, the percentage of joints with a diagnosis of disk displacement with reduction increased. Conversely, the percentage of joints with a diagnosis of disk displacement without reduction (in the group of patients with temporomandibular disorders) did not appear to be substantially affected by the 4 closed-mouth disk position criteria. Conclusions. These results suggest that the intermediate zone criterion for disk displacement is the more stringent criterion and the one that would yield the lowest number of false positives when the disk position is being judged in the closed-mouth sagittal view.

DOI： 10.1016/S1079-2104(98)90380-8

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC DENTAL RESEARCH  

It has been suggested that a sustained loading condition such as clenching could compress the temporomandibular joint (TMJ) articular soft tissues. However, there is still no clear understanding of how the TM joint articular tissues respond under compression. To answer this question, we performed in vitro indentation tests on fresh articular discs and cartilage-bone systems of the condyles of 10 Yorkshire pigs (aged 7 months) using a self-developed indentation tester. The indenter was 5 mm in diameter and was controlled by means of a computer-aided feedback mechanism. Bilateral condyles from the same mandible were uniformly prepared; one was used for measurements under sustained compression (SC) and the other for measurements under intermittent compression (IC). The displacements of the indenter induced by a SC of 10, 20, and 30 Newtons (N, units of force) for 10 min and by an IC, also of 10, 20, and 30 N, with one-second duration and two-second intervals for 10 min were measured by means of a displacement sensor with a resolution of 0.001 mm. From these data, the indentation curves of the articular discs and the cartilage-bone systems were calculated. Both the disc and the articular cartilage showed characteristic displacement vs. time curves-namely, an instantaneous deformation upon load application, followed by a time-dependent creep phase of asymptotically increasing deformation under constant load. However, the indentation curves of the two tissues were not identical: The deformation of the articular cartilage was dose-dependent, but that of the disc was not. Moreover, the articular cartilage deformed significantly less under IC than under SC. This difference was not found in the disc. It can be concluded that both the disc and the articular cartilage of the pig temporomandibular joint have viscoelastic properties against compression; however, the disc is stiffer than the articular cartilage.

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)  

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Although patient attrition might be a serious threat to the validity of treatment-outcome studies on temporomandibular disorders (TMD), studies on TMD patient attrition are scarce. Of the 1405 consecutive TMD patients examined in a recent 10-year period, 367 (26.1%) drop-out patients or patients identified with a control group were sampled. A mailed questionnaire failed to reach 41 patients, and 203 (62.3%) were returned. The questionnaire elicited information on reasons for dropping out, changes in symptoms, treatment received in other clinics after dropping out, present treatment needs, and current signs and symptoms. Dropouts were divided into two groups: (1) those who failed to show up for their first scheduled appointment after the clinical examination
(2) those who failed to complete treatment. A group of patients who were judged by the examiner not to need treatment were included as a control group. The main reasons for dropping out were environmental obstacles, perceived improvement of the disease, and dissatisfaction with services. Only 21.7% considered themselves to be in need of treatment, and only 10.3% had visited other clinics after dropping out. Only 8.9% complained of the continued aggravation of symptoms, whereas 57.6% reported improvement. In addition, pain, dysfunction, and daily activity limitation tended to improve with time, although temporomandibular joint noise tended to persist. These results suggest that TMD signs and symptoms tend to decrease in patients after dropping out, and that the natural fluctuation of TMD signs and symptoms should be taken into consideration when treating TMD.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Objective. This study was undertaken to investigate the potential of reducing observer variation through a calibration program. Study design. The study was based on three sets of randomly selected temporomandibular joint magnetic resonance images. Each set consisted of bilateral images from 20 consecutive patients with temporomandibular disorders. As a baseline, three well-experienced noncalibrated investigators interpreted the images individually for disk position and disk configuration. After the initial inter-pretation, interobserver agreement was calculated as a kappa index and presented to the examiners. On the same occasion, the investigators analyzed agreement between them on the criteria to be used. Results. Overall data in this study showed an increase in the frequency of interobserver agreement with regard to disk position after the calibration trials were instituted. With regard to disk configuration, substantial interindividual variations were observed even after the observers reached consensus as to the criteria to be used. Conclusions. These data suggest that after calibration trials, it is possible for three examiners to obtain reliable and reproducible results in reporting temporomandibular joint disk position on magnetic resonance images.

DOI： 10.1016/S1079-2104(97)90301-2

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It has been suggested that stabilization appliances and mandibular anterior repositioning appliances ivork by decompressing the temporomandibular joint. To indirectly test this assumption, tomograms of right temporomandibular joints of seven subjects were taken during comfortable closure and maximum clenching in maximum intercuspation and on the two types of occlusal appliances. Outlines of the condyle and the temporal fossa were automatically determined by an edge detection protocol. Upon comfortable closure, the anterior joint space dimension was reduced with stabilization appliances and mandibular anterior repositioning appliances. Upon maximum clenching, the minimum joint space dimension on stabilization appliances was equivalent to that seen in maximum intercuspation, while that on mandibular anterior repositioning appliances was substantially less (P &lt
.05). Findings do not indicate that these appliances induce an increase in joint space during clenching.

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

It has been suggested that stabilization appliances and mandibular anterior repositioning appliances ivork by decompressing the temporomandibular joint. To indirectly test this assumption, tomograms of right temporomandibular joints of seven subjects were taken during comfortable closure and maximum clenching in maximum intercuspation and on the two types of occlusal appliances. Outlines of the condyle and the temporal fossa were automatically determined by an edge detection protocol. Upon comfortable closure, the anterior joint space dimension was reduced with stabilization appliances and mandibular anterior repositioning appliances. Upon maximum clenching, the minimum joint space dimension on stabilization appliances was equivalent to that seen in maximum intercuspation, while that on mandibular anterior repositioning appliances was substantially less (P &lt
.05). Findings do not indicate that these appliances induce an increase in joint space during clenching.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Chroma, Inc.  

In order to discover the prevalence of signs and symptoms of temporomandibular disorders (TMD) in Japan, and the difference in the prevalence among various sex and age groups in the Japanese population, 672 individuals (304 males and 368 females, age range 20-92 years) were selected randomly in Okayama City, Japan, and were investigated by means of questionnaires and clinical examinations. The reported frequency of symptoms was: TMJ sounds 24%, facial-TMJ-jaw pain 11%, headache 27%, teeth clenching 30%, and grinding 34%. The percent frequency of the following signs was: impaired mouth opening 5%, clicking 46%, reciprocal clicking 20%, crepitus 19%, TMJ tenderness 6%, and masticatory muscle tenderness 21%. The subjects with TMJ clicking were more frequently females than males. TMD signs and symptoms were found to be common in all age groups, but they were fewer in the older than in the younger age group. The younger-aged subjects with clicking appeared with significant frequency, whereas crepitus was populated with significant frequency by the oldest age group. Copyright © 1996 by CHROMA, Inc.

DOI： 10.1080/08869634.1996.11745962

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Objective. To measure the effect of unilateral sustained clenching on the temporomandibular joints, changes in the minimum joint space dimension were assessed. Study design. Ten healthy subjects performed a sustained clench on a bite force transducer in the first molar region for 5 minutes with a constant force of 170 N. Three separate sagittal tomograms were bilaterally obtained with the transducer in place before clenching and during the beginning and at the end of the contraction. Changes were quantified with a computerized image analysis system. Results. The minimum joint space of the contralateral temporomandibular joint was significantly reduced both at the beginning and at the end of the contraction task. Further the minimum joint space was also significantly less at the end than at the beginning of the contraction even though bite force level was identical. The ipsilateral condyle images showed no significant shift in the minimum joint space. Conclusions. These data suggest that unilateral molar clenching induces a significant reduction of the minimum joint soace in the contralateral temooromandibular joint and a sustained condition remarkably increases this change. Copyright © 1996 by Mosby-Year Book, Inc.

DOI： 10.1016/S1079-2104(96)80435-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Mosby Inc.  

Objective. To measure the effect of unilateral sustained clenching on the temporomandibular joints, changes in the minimum joint space dimension were assessed. Study design. Ten healthy subjects performed a sustained clench on a bite force transducer in the first molar region for 5 minutes with a constant force of 170 N. Three separate sagittal tomograms were bilaterally obtained with the transducer in place before clenching and during the beginning and at the end of the contraction. Changes were quantified with a computerized image analysis system. Results. The minimum joint space of the contralateral temporomandibular joint was significantly reduced both at the beginning and at the end of the contraction task. Further the minimum joint space was also significantly less at the end than at the beginning of the contraction even though bite force level was identical. The ipsilateral condyle images showed no significant shift in the minimum joint space. Conclusions. These data suggest that unilateral molar clenching induces a significant reduction of the minimum joint soace in the contralateral temooromandibular joint and a sustained condition remarkably increases this change. Copyright © 1996 by Mosby-Year Book, Inc.

DOI： 10.1016/S1079-2104(96)80435-5

Scopus

PubMed

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DOI： 10.2186/jjps.40.702

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：The Japan Prosthodontic Society  

The IMZ implant system incorporates stress-absorbing elements, such as theintramobile element (DME). There are varying reports regarding the characteristics of the DME :however, its effectiveness is still controversial.In order to evaluate the effectiveness of the stress-absorbing elements under dynamic loadingconditions, the stress-transfer characteristics around a single freestanding IMZ implant were inves-tigated with three types of internal elements : an DME made of polyoxymethylene, an intramobileconnector (IMC) consisting of a polyoxymethylene head and titanium screw, and a metal element(Metal-E) made of stainless steel.The vertical (10-kgf) and horizontal (2-kgf) dynamic forces applied to the surface of thesuperstructure and the strain values around the implant were measured with the strain gauges.The results were as follows :1. Under axial dynamic force, the three types of elements had no significant difference in thestresses around a single freestanding implant.2. Under vertical tilting dynamic forces, a more uniform stress around a single freestandingimplant was observed with IME and IMC than Metal-E.3. Under horizontal dynamic force, a more uniform stress around a single freestanding implantwas observed with DME and IMC than Metal-E.The stress-absorbing elements were significantly effective under the dynamic conditions, whilethey were not effective under the static conditions.

DOI： 10.2186/jjps.37.744

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/1994186057

DOI： 10.11277/stomatology1952.42.159

J-GLOBAL

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J-GLOBAL

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J-GLOBAL

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Language：Japanese   Publisher：The Japan Prosthodontic Society  

Recently, osseoizategrated dental implants have come to be used more and more in thetreatment of edentulism. Osseointegration has been found to achieve better results than fibroosseous integration : however, it has been suggested that excessive and/or concentrated stressesmay cause resorption of the surrounding bone.To address this problem, the IMZ implant system incorporates stress-absorbing elements, suchas the intramobile element (DME) . There are varying reports regarding the characteristics of theIME, however, and its effectiveness is still controversial.This study compares the stress-transfer characteristics around a single freestanding IMZimplant with three types of internal elements : an IME made of polyoxymethylene, an intramobileconnector (IMC) consisting of a polyoxymethylene head and titanium screw, and a metal element(Metal-E) made of stainless steel. An IMZ implant ( 75 4 X13 mm) and five strain gauges (KyowaInc.) around the implant were enxbedded in an acrylic resin block (3X3X3 cm). The vertical (10and 15 kgf) and horizontal (3 and 5 kgf) static forces applied to the surface of the superstructure andthe strain values around the implant were measured.The results are as follows :1. Under vertical forces, among the three types of elements no significant difference in thestresses around a single freestanding implant was found.2. Under horizontal forces, a more uniform stress around a single freestanding implant withthe Metal-E was observed. When using the DME, there was a greater stress concentration on theupper-oppressive side of the implant. The action of the IMC appeared to be midway between the IME and Metal-E. 3. The IME fractured after several applicatioins of 5-kgf horizontal force.

DOI： 10.2186/jjps.36.1102

CiNii Article

CiNii Books

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Other Link： http://search.jamas.or.jp/link/ui/1994025256

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Language：Japanese   Publisher：岡山歯学会  

生体の筋活動をもとに顎関節部負荷を算出しうる生物力学的近似モデルを作成し,片側噛みしめ時の顎関節部負荷に影響を及ぼす各因子について解析した.1)左右筋力比が変化すると顎関節部負荷は大きく影響を受け,その負荷の絶対量は左右で逆転する可能性がある.2)筋合力の位置により後方に位置するに従って両側顎関節部に加わる負荷は増大し,その変化率は噛みしめ側顎関節が大きい.3)下顎頭間距離が大きくなるにつれて噛みしめ側と非噛みしめ側の顎関節部負荷の差は縮小するが,他の因子に比べてその影響は小さい.4)顎関節部負荷は歯列弓の幅によって影響を受け,歯列弓の幅が大きくなると非噛みしめ側の負荷が増加する.5)噛みしめ力を一定とした場合,咬合点の位置が後方に移るに従って両側顎関節に加わる圧縮力は減少し,特に噛みしめ側の負荷は,咬合点がある一定の限度を越えて後方に位置すると圧縮力から牽引力になる

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：KARGER  

Web of Science

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CiNii Article

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Responsible for pages：57-63   Language：Japanese

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Responsible for pages：43-47   Language：Japanese

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Responsible for pages：17-37   Language：Japanese

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Responsible for pages：pp39-40   Language：Japanese

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Responsible for pages：pp1-85   Language：Japanese

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