Faculty Profiles - KUBOKI Takuo

Papers - KUBOKI Takuo

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BMP-2 generates a functional bone marrow niche by inducing the differentiation of local mesenchymal cells into CAR cells

Mitsuaki Ono, Ikue Tosa, Anh Tuan Dang, Ziyi Wang, Maiko Kimura, Wakana Kitagawa, Kei Ishibashi, Hang Thuy Do, Kun Zhao, Emilio Satoshi Hara, Noboru Asada, Takashi Nagasawa, Toshitaka Oohashi, Naoya Ohara, Takuo Kuboki

Blood Advances 2025.3

Publishing type：Research paper (scientific journal) Publisher：American Society of Hematology

Ectopic bone marrow (eBM) holds tremendous potential as an artificial organ, serving not only in stem cell transplantation therapies but also as a controlled experimental system for analyzing cellular dynamics and interactions between cells and the matrix during the formation, maintenance, and aging of bone marrow (BM). Although bone morphogenetic protein (BMP)-2 has been reported to induce eBM formation, it remains unproven whether BMP-2 induced eBM (BMP-eBM) can provide a functional BM niche that is comparable to native BM in long bones (LB-BM). In this study, through the use of single-cell RNA sequencing and transplantation models, we demonstrate for the first time that BMP-eBM displays a microstructure, cellular composition, and functional hematopoiesis similar to LB-BM. BMP-eBM establishes an optimized microenvironment capable of supporting hematopoietic stem cells (HSCs) and CXC-chemokine-ligand-12 (CXCL12)-abundant reticular (CAR) cells, which are critical components of the BM niche. Significantly, BMP-eBM was able to restore survival in irradiated mice. Through parabiosis and cell transplantation experiments, we identified that in situ adipose tissue-derived CD51highCxcl12-GFP- cells are the principal source of CAR cells within BMP-eBM. Furthermore, BMP-eBM can be isolated and, after preconditioning, re-transplanted as an independent, functional hematopoietic organ. In conclusion, our study confirms that BMP-eBM functions effectively as a hematopoietic organ, capable of supporting and maintaining a functional BM niche. These findings underscore BMP-2 as a crucial molecule for eBM generation and suggest its potential for addressing BM-related diseases and for use as a platform for in vitro and ex vivo biomedical applications.

DOI： 10.1182/bloodadvances.2024014062

Optimizing β-TCP with E-rhBMP-2-infused fibrin for vertical bone regeneration in a mouse calvarium model

Kun Zhao, Mitsuaki Ono, Xindi Mu, Ziyi Wang, Shichao Xie, Tomoko Yonezawa, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Toshitaka Oohashi

Regenerative Biomaterials 12 2025.1

Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

Abstract

Effective reconstruction of large bone defects, particularly in thickness, remains one of the major challenges in orthopedic and dental fields. We previously produced an Escherichia coli-based industrial-scale GMP-grade recombinant human bone morphogenetic protein-2 (E-rhBMP-2) and showed that the combination of E-rhBMP-2 with beta-tricalcium phosphate (β-TCP/E-rhBMP-2) can effectively promote bone reconstruction. However, the limited mechanical strength and poor morphology retention of β-TCP granules are key points that need optimization to obtain more effective grafts and further expand its clinical applications. Therefore, we combined β-TCP/E-rhBMP-2 with fibrin gel to enhance its mechanical properties and usability for vertical bone regeneration. We investigated the mechanical properties and vertical bone regeneration effects of the materials applied, with or without fibrin containing E-rhBMP-2, in a calvarial defect model in mice. Compression tests were conducted to assess the initial stability of the materials. Scanning electron microscopy and Fourier transform infrared spectroscopy were conducted to characterize the presence of fibrin on the scaffold. After 4 and 12 weeks of implantation, micro-computed tomography and histological and immunofluorescent analyses were performed to assess the morphology and volume of the newly formed bone. The fibrin-containing groups had significantly higher initial mechanical strength and higher ability to maintain their morphology in vivo compared to the counterparts without fibrin. However, fibrin gel alone suppressed the bone formation ability of β-TCP/E-rhBMP-2 whereas the presence of high doses of E-rhBMP-2 in fibrin gel resulted in material resorption and enhanced new bone formation. In conclusion, fibrin gel significantly improved the mechanical strength and surgical manageability of the β-TCP/E-rhBMP-2 scaffold, and the addition of E-rhBMP-2 to the fibrin gel further enhanced the vertical bone regeneration and initial structural integrity of the scaffold.

DOI： 10.1093/rb/rbae144

Other Link： https://academic.oup.com/rb/article-pdf/doi/10.1093/rb/rbae144/61841803/rbae144.pdf

Association among prosthodontic treatment, dietary diversity, and ingestible food profile in older outpatients with missing teeth

Kazuki Sakamoto, Aya Kimura-Ono, Yoko Kurosaki, Takuya Mino, Shinsuke Nakagawa, Yuji Shimomura, Kou Omori, Takaharu Higuchi, Eri Koyama, Kumiko Nawachi, Kana Tokumoto, Yuji Tsuchiyama, Tokihiro Fukutoku, Mitsuaki Ono, Takuo Kuboki

Journal of Prosthodontic Research 2025

既製NSVの改良開発(第一報) 設計と形状

庄賀春生, 宮崎文伸, 太田圭二, 松岸諒, 桑原実穂, 吉實舞, 兒玉直紀, 田中祐貴, 古西隆之, 藤田隼平, 瀬島淳一, 窪木拓男

日本口腔顎顔面技工学会会誌 24 ( 1 ) 46,51 - 52 2024.12

Implant-supported fixed prostheses with cantilever: a systematic review and meta-analysis. International journal

Yusuke Kondo, Kiyoshi Sakai, Hajime Minakuchi, Takuya Horimai, Takuo Kuboki

International journal of implant dentistry 10 ( 1 ) 57 - 57 2024.11

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

PURPOSE: This systematic review (SR) aimed to investigate whether the presence of a cantilever affects the results of implant treatment for partial edentulism, including an analysis of the anterior and posterior regions of the dental arches. METHODS: An electronic search was performed, and original articles published between 1995 and November 2023 were included. The outcomes were the implant survival rate, patient satisfaction, occurrence of mechanical complications, and marginal bone loss around the implants. Two SR members independently examined the validity of the studies, extracted evidence from the included studies, and performed risk of bias assessment, comprehensive evidence evaluation, and meta-analysis. RESULTS: Nine studies met our inclusion criteria. Implant survival rate tended to be lower in the cantilever group, and marginal bone loss tended to be higher in the cantilever group; however, there was no significant difference. There was no significant difference in patient satisfaction based on the presence or absence of a cantilever. Moreover, the incidence of mechanical complications was significantly higher in the cantilever group. According to the analysis of anterior and posterior regions, implant survival rate tended to be lower in the cantilever group of the posterior region, and marginal bone loss around the implants tended to be higher in the cantilever group of the anterior region. CONCLUSION: Implant-supported fixed prostheses with cantilevers did not negatively affect implant survival rate, marginal bone loss, or patient satisfaction. However, the incidence of mechanical complications significantly increased in the cantilever group.

DOI： 10.1186/s40729-024-00573-8

Macrophages modulate mesenchymal stem cell function via tumor necrosis factor alpha in tooth extraction model. Reviewed International journal

Aung Ye Mun, Kentaro Akiyama, Ziyi Wang, Jiewen Zhang, Wakana Kitagawa, Teisaku Kohno, Ryuji Tagashira, Kei Ishibashi, Naoya Matsunaga, Tingling Zou, Mitsuaki Ono, Takuo Kuboki

JBMR plus 8 ( 8 ) ziae085 2024.8

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

Mesenchymal stem cells (MSCs) and macrophages collaboratively contribute to bone regeneration after injury. However, detailed mechanisms underlying the interaction between MSCs and inflammatory macrophages (M1) remain unclear. A macrophage-depleted tooth extraction model was generated in 5-wk-old female C57BL/6J mice using clodronate liposome (12.5 mg/kg/mouse, intraperitoneally) or saline injection (control) before maxillary first molar extraction. Mice were sacrificed on days 1, 3, 5, 7, and 10 after tooth extraction (n = 4). Regenerated bone volume evaluation of tooth extraction socket (TES) and histochemical analysis of CD80+M1, CD206+M2 (anti-inflammatory macrophages), PDGFRα+MSC, and TNF-α+ cells were performed. In vitro, isolated MSCs with or without TNF-α stimulation (10 ng/mL, 24 h, n = 3) were bulk RNA-sequenced (RNA-Seq) to identify TNF-α stimulation-specific MSC transcriptomes. Day 7 micro-CT and HE staining revealed significantly lower mean bone volume (clodronate vs control: 0.01 mm3 vs 0.02 mm3, p<.0001) and mean percentage of regenerated bone area per total TES in clodronate group (41.97% vs 54.03%, p<.0001). Clodronate group showed significant reduction in mean number of CD80+, TNF-α+, PDGFRα+, and CD80+TNF-α+ cells on day 5 (306.5 vs 558.8, p<.0001; 280.5 vs 543.8, p<.0001; 365.0 vs 633.0, p<.0001, 29.0 vs 42.5, p<.0001), while these cells recovered significantly on day 7 (493.3 vs 396.0, p=.0004; 479.3 vs 384.5, p=.0008; 593.0 vs 473.0, p=.0010, 41.0 vs 32.5, p=.0003). RNA-Seq analysis showed that 15 genes (|log2FC| > 5.0, log2TPM > 5) after TNF-α stimulation were candidates for regulating MSC's immunomodulatory capacity. In vivo, Clec4e and Gbp6 are involved in inflammation and bone formation. Clec4e, Gbp6, and Cxcl10 knockdown increased osteogenic differentiation of MSCs in vitro. Temporal reduction followed by apparent recovery of TNF-α-producing M1 macrophages and MSCs after temporal macrophage depletion suggests that TNF-α activated MSCs during TES healing. In vitro mimicking the effect of TNF-α on MSCs indicated that there are 15 candidate MSC genes for regulation of immunomodulatory capacity.

DOI： 10.1093/jbmrpl/ziae085

The cell membrane as biofunctional material for accelerated bone repair. Reviewed International journal

Emi Hatano, Nahid Akhter, Risa Anada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Hiroshi Kamioka, Masahiro Okada, Takuya Matsumoto, Emilio Satoshi Hara

Acta biomaterialia 2024.7

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

The cell (plasma) membrane is enriched with numerous receptors, ligands, enzymes, and phospholipids that play important roles in cell-cell and cell-extracellular matrix interactions governing, for instance, tissue development and repair. We previously showed that plasma membrane nanofragments (PMNFs) act as nucleation sites for bone formation in vivo, and induce in vitro mineralization within 1 day. In this study, we optimized the methods for generating, isolating, and applying PMNFs as a cell-free therapeutic to expedite bone defect repair. The PMNFs were isolated from different mouse cell lines (chondrocytes, osteoblasts, and fibroblasts), pre-conditioned, lyophilized, and subsequently transplanted into 2 mm critical-sized calvarial defects in mice (n = 75). The PMNFs from chondrocytes, following a 3-day pre-incubation, significantly accelerated bone repair within 2 weeks, through a coordinated attraction of macrophages, endothelial cells, and osteoblasts to the healing site. In vitro experiments confirmed that PMNFs enhanced cell adhesion. Comparison of the PMNF efficacy with phosphatidylserine, amorphous calcium phosphate (ACP), and living cells confirmed the unique ability of PMNFs to promote accelerated bone repair. Importantly, PMNFs promoted nearly complete integration of the regenerated bone with native tissue after 6 weeks (% non-integrated bone area = 15.02), contrasting with the partial integration (% non-integrated bone area = 56.10; p < 0.01, Student's test) with transplantation of ACP. Vickers microhardness tests demonstrated that the regenerated bone after 6 weeks (30.10 ± 1.75) exhibited hardness similar to native bone (31.07 ± 2.46). In conclusion, this is the first study to demonstrate that cell membrane can be a promising cell-free material with multifaceted biofunctional properties that promote accelerated bone repair. STATEMENT OF SIGNIFICANCE.

DOI： 10.1016/j.actbio.2024.07.037

Long-term follow-up of a patient with Parkinson's disease under nursing care after replacement of fixed implant-supported prostheses with an implant overdenture: a case report. Reviewed International journal

Kana Tokumoto, Takuya Mino, Ikue Tosa, Ko Omori, Michiyo Yamamoto, Kazuki Takaoka, Kenji Maekawa, Takuo Kuboki, Hiromitsu Kishimoto

International journal of implant dentistry 10 ( 1 ) 37 - 37 2024.7

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

BACKGROUND: In older patients with progressive neurodegeneration, replacing fixed implant-supported prostheses (FIP) with implant overdentures (IOD) has been proposed to prevent future mucosal injury and create an oral environment that is easier for caregivers to clean. However, there have been no reports on the progress after replacing FIP with IOD. In this report, we present the progress of an older patient with Parkinson's disease in whom FIP was replaced with IOD. CASE PRESENTATION: An 81-year-old male patient with Parkinson's disease presented to our outpatient clinic with bruxism and crossbites. FIPs, with five Brånemark system implants, were placed in the bilateral lower molars. The FIP was replaced with an IOD with two locator attachments to create an oral environment that was easier for caregivers to clean and allow easy recovery of masticatory function if residual teeth were fractured in the care environment. As his systemic condition deteriorated, treatment was changed from outpatient to in-home visits. During dental care visits, professional oral cleaning and denture repair were continued, and good nutritional status was maintained. However, the patient developed cholecystitis and was hospitalized. During hospitalization, gastrostomy was performed because he developed aspiration pneumonia. After discharge from the hospital, the patient remained in bed all day and could not wear an IOD, resulting in buccal mucosa ulceration due to abrasion of the locator abutment. We decided to replace the abutment with cover screws; however, not all the implants could sleep submucosally. Although regular oral cleaning was resumed, new ulcers developed even when cover screws were installed. Additionally, swelling and drainage were observed at the peri-implant mucosal site where peri-implantitis had once occurred during an outpatient visit. The patient was readmitted to the hospital for a urinary tract infection, and subsequent visits were abandoned. CONCLUSIONS: By replacing FIP with IOD in an older patient with Parkinson's disease, we addressed a barrier to caregiver-provided oral management. The removable prosthesis facilitated smooth oral care by caregivers and functional recovery in the event of trouble with residual teeth. However, it could not completely avoid the recurrence of buccal mucosal ulcers or peri-implantitis.

DOI： 10.1186/s40729-024-00557-8

Medical-dental collaboration on an exploratory research project on the correlation between cognitive and oral function: The ECCO project. Reviewed

Kenji Fueki, Yuta Manabe, Keiichi Sasaki, Katsuhiko Kimoto, Mamoru Hashimoto, Takayuki Ueda, Kumiko Utsumi, Tomohisa Ishikawa, Kazuyoshi Baba, Manabu Ikeda, Takuo Kuboki

Journal of prosthodontic research 2024.7

Local E-rhBMP-2/β-TCP Application Rescues Osteocyte Dendritic Integrity and Reduces Microstructural Damage in Alveolar Bone Post-Extraction in MRONJ-like Mouse Model Reviewed International journal

Anh Tuan Dang, Mitsuaki Ono, Ziyi Wang, Ikue Tosa, Emilio Satoshi Hara, Akihiro Mikai, Wakana Kitagawa, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

International Journal of Molecular Sciences 25 ( 12 ) 6648 - 6648 2024.6

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

Inverse genetics tracing the differentiation pathway of human chondrocytes Reviewed

H.T. Do, M. Ono, Z. Wang, W. Kitagawa, A.T. Dang, T. Yonezawa, T. Kuboki, T. Oohashi, S. Kubota

Osteoarthritis and Cartilage 2024.6

パーキンソン病患者の固定性インプラント補綴を可撤性へ置換後に介護現場でトラブルを生じた症例

徳本佳奈, 窪木拓男

日本老年歯科医学会総会・学術大会プログラム・抄録集 35回認定P - 08 2024.6

Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa Reviewed International journal

Xindi Mu, Mitsuaki Ono, Ha Thi Thu Nguyen, Ziyi Wang, Kun Zhao, Taishi Komori, Tomoko Yonezawa, Takuo Kuboki, Toshitaka Oohashi

Cells 13 ( 10 ) 807 - 807 2024.5

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

天然歯支台のプロビジョナルレストレーションと支台歯の三次元表面形状像を基準に理想的な最終補綴装置をデザインするデジタルワークフロー

徳本佳奈, 三野卓哉, 黒崎陽子, 和泉幸治, 仲野友人, 瀬島淳一, 大野彩, 前川賢治, 窪木拓男

日本デジタル歯科学会誌 14 ( 1 ) 81 - 81 2024.5

Associations between measured masticatory function and cognitive status: A systematic review Reviewed International journal

Kenji Maekawa, Yoshiko Motohashi, Kentaro Igarashi, Takuya Mino, Yasuhiko Kawai, Youngnam Kang, Toshihiro Hirai, Takuo Kuboki

Gerodontology 2024.3

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

Does maintaining the number of present and functional teeth benefit the longevity of life in older people requiring nursing care?: A prospective cohort study. Reviewed

Eri Koyama, Aya Kimura-Ono, Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Michiyo Yamamoto, Shinsuke Nakagawa, Suguru Osaka, Kumiko Nawachi, Mami Inoue-Minakuchi, Mitsuaki Ono, Hajime Minakuchi, Kenji Maekawa, Takuo Kuboki

Journal of prosthodontic research 2024.3

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

Age-Related Effects on MSC Immunomodulation, Macrophage Polarization, Apoptosis, and Bone Regeneration Correlate with IL-38 Expression. Reviewed International journal

Jiewen Zhang, Kentaro Akiyama, Aung Ye Mun, Ryuji Tagashira, Tingling Zou, Naoya Matsunaga, Teisaku Kohno, Takuo Kuboki

International journal of molecular sciences 25 ( 6 ) 2024.3

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

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

DO ORAL CARE AND REHABILITATION IMPROVE COGNITIVE FUNCTION? A SYSTEMATIC REVIEW OF CLINICAL STUDIES. Reviewed International journal

Yuka Inamochi, Yoichiro Ogino, Kae Harada, Kenji Fueki, Yasunori Ayukawa, Masahiro Nishimura, Kenji Maekawa, Youngnam Kang, Toshihiro Hirai, Takuo Kuboki

The journal of evidence-based dental practice 24 ( 1 ) 101948 - 101948 2024.3

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

認知機能と口腔機能の相関に関する医師・歯科医師の意識調査医科歯科連携ECCOプロジェクト

笛木賢治, 眞鍋雄太, 佐々木啓一, 橋本衛, 木本克彦, 石川智久, 上田貴之, 内海久美子, 釘宮嘉浩, 白石成, 安部友佳, 稲用友佳, 馬場一美, 窪木拓男, 池田学

老年精神医学雑誌 35 ( 3 ) 283 - 290 2024.3

Language：Japanese Publisher：(株)ワールドプランニング

日本老年精神医学会と日本補綴歯科学会が共同で実施しているECCOプロジェクトでは,認知機能と口腔機能との関連について連携研究を進めている.本研究では,新たな研究課題を探索するために,認知症専門医と歯科医師を対象として,認知機能と口腔機能の相関に関する意識調査を行った.その結果,歯の喪失と口腔機能の低下が認知機能の低下と認知症の発症に関連する臨床経験,認知症の行動・心理症状(BPSD)が口腔の問題と関連する臨床経験,歯科治療により認知機能が改善した臨床経験を有する割合は医師と歯科医師で同程度であり,認知機能と口腔機能の関連は医師と歯科医師で共通認識であることが明らかになった.また,認知症の先制予防としてオーラルフレイルの改善に対する期待が高かった.以上の結果をもとに,BPSDと口腔機能との関連を解明する研究と口腔機能への介入が認知機能に及ぼす影響に関する研究をECCOプロジェクトの今後の課題に設定した.(著者抄録)

Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J02464&link_issn=&doc_id=20240417110008&doc_link_id=%2Faj2rsizd%2F2024%2F003503%2F009%2F0283-0290%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faj2rsizd%2F2024%2F003503%2F009%2F0283-0290%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Tooth morphology fusion technique is more accurate than conventional technique in transferring morphology of provisional to definitive screw-retained, implant-supported crown: A preliminary intervention study. Reviewed

Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Koji Izumi, Hiroshi Mitsumune, Kenji Maekawa, Akihiro Ueda, Tomohito Nakano, Junichi Sejima, Aya Kimura-Ono, Takuo Kuboki

Journal of prosthodontic research 68 ( 1 ) 139 - 146 2024.1

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

A novel brief questionnaire using a face rating scale to assess dental anxiety and fear Reviewed

Takuya Mino, Aya Kimura-Ono, Hikaru Arakawa, Kana Tokumoto, Yoko Kurosaki, Yoshizo Matsuka, Kenji Maekawa, Takuo Kuboki

The Journal of Advanced Prosthodontics 16 ( 4 ) 244 - 244 2024

Positive Regulation of S-Adenosylmethionine on Chondrocytic Differentiation via Stimulation of Polyamine Production and the Gene Expression of Chondrogenic Differentiation Factors Reviewed International journal

Loc Dinh Hoang, Eriko Aoyama, Miki Hiasa, Hiroshi Omote, Satoshi Kubota, Takuo Kuboki, Masaharu Takigawa

International Journal of Molecular Sciences 24 ( 24 ) 17294 - 17294 2023.12

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

可撤性上部構造へ置換後のパーキンソン病患者にインプラントに起因するトラブルが生じた介護現場での1例

徳本佳奈, 三野卓哉, 高岡一樹, 前川賢治, 窪木拓男, 岸本裕充

日本口腔リハビリテーション学会雑誌 36 ( 1 ) 67 - 67 2023.12

可撤性上部構造へ置換後のパーキンソン病患者にインプラントに起因するトラブルが生じた介護現場での1例

徳本佳奈, 三野卓哉, 高岡一樹, 前川賢治, 窪木拓男, 岸本裕充

日本口腔リハビリテーション学会雑誌 36 ( 1 ) 67 - 67 2023.12

Accuracy of a novel modified single computed tomography scanning method for assisting dental implant placement: a retrospective observational study. Reviewed International journal

Hiroaki Shimizu, Takuya Mino, Yoko Kurosaki, Hikaru Arakawa, Kana Tokumoto, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki

International journal of implant dentistry 9 ( 1 ) 42 - 42 2023.11

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

パーキンソン病患者の固定性インプラント補綴を可撤性へ置換したが介護現場でのインプラントに起因するトラブルを回避できなかった1例

徳本佳奈, 三野卓哉, 土佐郁恵, 高岡一樹, 前川賢治, 窪木拓男, 岸本裕充

日本口腔インプラント学会誌 36 ( 特別号 ) P - 44 2023.9

暫間上部構造形状を最終上部構造へ反映させるTooth Morphology Fusion Techniqueの有効性に関する介入研究

三野卓哉, 黒崎陽子, 徳本佳奈, 和泉幸治, 仲野友人, 大野彩, 窪木拓男, 前川賢治

日本口腔インプラント学会誌 36 ( 特別号 ) O - 8 2023.9

暫間上部構造形状を最終上部構造へ反映させるTooth Morphology Fusion Techniqueの有効性に関する介入研究

三野卓哉, 黒崎陽子, 徳本佳奈, 和泉幸治, 仲野友人, 大野彩, 窪木拓男, 前川賢治

日本口腔インプラント学会誌 36 ( 特別号 ) O - 8 2023.9

パーキンソン病患者の固定性インプラント補綴を可撤性へ置換したが介護現場でのインプラントに起因するトラブルを回避できなかった1例

徳本佳奈, 三野卓哉, 土佐郁恵, 高岡一樹, 前川賢治, 窪木拓男, 岸本裕充

日本口腔インプラント学会誌 36 ( 特別号 ) P - 44 2023.9

開口障害を有するがんサバイバーのための加工した歯ブラシの歯垢除去効果に関する検討 Reviewed

藤代万由, 松崎久美子, 佐々木禎子, 梶谷明子, 吉田陽子, 宮崎文伸, 三浦留美, 窪木拓男

日本歯科衛生学会雑誌 18 ( 1 ) 153 - 153 2023.8

認知機能と口腔機能の相関に関する探索的研究(ECCO)プロジェクト活動の趣旨と内容 Reviewed

笛木賢治, 佐々木啓一, 眞鍋雄太, 大本克彦, 窪木拓男, 上田貴之, 安部友佳, 稲用友佳, 釘宮嘉浩, 白石成, 齋藤壮, 小林琢也, 橋本衛, 石川智久, 内海久美子, 池田学, 馬場一美, 公益社団法人日本補綴歯科学会研究企画推進委員会

日本補綴歯科学会誌 15 ( 1 ) 72 - 78 2023.1

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)

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

Medical-Dental collaboration: Exploratory research project on the Correlation between Cognitive and Oral function (ECCO): background and research activity Reviewed

Kenji Fueki, Keiichi Sasaki, Yuta Manabe, Katsuhiko Kimoto, Takuo Kuboki, Takayuki Ueda, Yuka Abe, Yuka Inamochi, Yoshihiro Kugimiya, Naru Shiraishi, Takashi Saito, Takuya Kobayashi, Mamoru Hashimoto, Tomohisa Ishikawa, Kumiko Utsumi, Manabu Ikeda, Kazuyoshi Baba

Annals of Japan Prosthodontic Society 15 ( 1 ) 72 - 78 2023

Dilemma of cohort study-A concept of early disease markers for measured risk factors. Invited Reviewed

Takuo Kuboki

Journal of prosthodontic research 67 ( 4 ) vi 2023

コロナ禍における老人介護施設での口腔栄養関連サービスに関するPBL演習 Reviewed

前田あずさ,縄稚久美子,菊谷武,兒玉直紀,萬田陽介,窪木拓男

岡山歯学会雑誌 41 ( 2 ) 21 - 33 2022.12

Impact of number of functional teeth on independence of Japanese older adults. Reviewed

Kenji Maekawa, Tomoko Ikeuchi, Shoji Shinkai, Hirohiko Hirano, Masahiro Ryu, Katsushi Tamaki, Hirofumi Yatani, Takuo Kuboki, Aya Kimura-Ono, Takeshi Kikutani, Takashi Suganuma, Yasunori Ayukawa, Tomoya Gonda, Toru Ogawa, Masanori Fujisawa, Shoichi Ishigaki, Yutaka Watanabe, Akihiko Kitamura, Yu Taniguchi, Yoshinori Fujiwara, Ayako Edahiro, Yuki Ohara, Junichi Furuya, Junko Nakajima, Kento Umeki, Kentaro Igarashi, Yasuhiro Horibe, Yoshihiro Kugimiya, Yasuhiko Kawai, Hideo Matsumura, Tetsuo Ichikawa, Shuji Ohkawa, Kazuyoshi Baba

Geriatrics & gerontology international 22 ( 12 ) 1032 - 1039 2022.12

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

欠損補綴治療が高齢者の食品摂取の多様性や摂取可能食品に与える影響 Reviewed

坂本和基, 大野彩, 三野卓哉, 黒崎陽子, 下村侑司, 大森江, 樋口隆晴, 小山絵理, 徳本佳奈, 縄稚久美子, 窪木拓男

日本口腔リハビリテーション学会雑誌 35 ( 1 ) 79 - 80 2022.12

欠損補綴治療が高齢者の食品摂取の多様性や摂取可能食品に与える影響

坂本和基, 大野彩, 三野卓哉, 黒崎陽子, 下村侑司, 大森江, 樋口隆晴, 小山絵理, 徳本佳奈, 縄稚久美子, 窪木拓男

日本口腔リハビリテーション学会雑誌 35 ( 1 ) 79 - 80 2022.12

卒前臨床技術教育でデジタル光学印象を経験させる相互実習の導入

下村侑司, 土山雄司, 窪木慎野介, 松永直也, 北川若奈, 黄野頂策, 石橋啓, 田仲由希恵, 大森江, 水口真実, 中川晋輔, 三木春奈, 三野卓哉, 前田あずさ, 縄稚久美子, 秋山謙太郎, 水口一, 窪木拓男

岡山歯学会雑誌 41 ( 2 ) 58 - 59 2022.12

Therapeutic effects of peptide P140 in a mouse periodontitis model. Reviewed International journal

Kentaro Akiyama, Kyaw Thu Aung, Laura Talamini, Olivier Huck, Takuo Kuboki, Sylviane Muller

Cellular and molecular life sciences : CMLS 79 ( 10 ) 518 - 518 2022.9

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

老人介護施設における要介護高齢者や介護職員と歯学部生を電子的に繋いだPBL演習の取組

縄稚久美子, 前田あずさ, 兒玉直紀, 萬田陽介, 菊谷武, 窪木拓男

老年歯科医学 37 ( 2 ) 162 - 162 2022.9

Rating criteria to evaluate student performance in digital wax-up training using multi-purpose software. Reviewed International journal

Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Takaharu Higuchi, Shinichi Nakanoda, Ken Numoto, Ikue Tosa, Aya Kimura-Ono, Kenji Maekawa, Tae Hyung Kim, Takuo Kuboki

The journal of advanced prosthodontics 14 ( 4 ) 203 - 211 2022.8

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

Prosthodontic treatment can improve the ingestible food profile in Japanese adult outpatients. Reviewed

Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Kumiko Nawachi, Masanori Fujisawa, Hironobu Sato, Hideki Aita, Shigeto Koyama, Masayuki Hideshima, Yuji Sato, Hiroyuki Wake, Kan Nagao, Yorika Kodaira-Ueda, Katsushi Tamaki, Shinsuke Sadamori, Kazuhiro Tsuga, Yasuhiro Nishi, Takashi Sawase, Hisashi Koshino, Shin-Ichi Masumi, Kaoru Sakurai, Kanji Ishibashi, Takashi Ohyama, Yasumasa Akagawa, Toshihiro Hirai, Keiichi Sasaki, Kiyoshi Koyano, Hirofumi Yatani, Hideo Matsumura, Tetsuo Ichikawa, Shuji Ohkawa, Kazuyoshi Baba

Journal of prosthodontic research 67 ( 2 ) 189 - 195 2022.5

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

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

Fixed Partial Denture Designed by Combining the Whole 3D Digital Surface Morphology of the Provisional Restoration and Abutment Teeth Surfaces.

Kana Tokumoto, Takuya Mino, Yoko Kurosaki, Koji Izumi, Kenji Maekawa, Tomohito Nakano, Junichi Sejima, Akihiro Ueda, Aya Kimura-Ono, Tae Hyung Kim, Takuo Kuboki

Acta medica Okayama 76 ( 1 ) 79 - 84 2022.2

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

White discharge formation following a subepithelial connective tissue graft for anterior fixed partial denture pontics: A case report based on clinical and histological findings. Reviewed

Norimi Oda, Mitsuaki Ono, Wataru Sonoyama, Taichiro Morimoto, Ikue Tosa, Shuji Nousho, Keisuke Nakano, Takuo Kuboki

Journal of prosthodontic research 66 ( 1 ) 184 - 192 2022.1

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

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

Effectiveness of the socket shield technique in dental implant: A systematic review. Reviewed

Toru Ogawa, Ratri M Sitalaksmi, Makiko Miyashita, Kenji Maekawa, Masahiro Ryu, Aya Kimura-Ono, Takeshi Suganuma, Takeshi Kikutani, Masanori Fujisawa, Katsushi Tamaki, Takuo Kuboki

Journal of prosthodontic research 66 ( 1 ) 12 - 18 2022.1

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

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

Preclinical bioequivalence study of E.coli-derived rhBMP-2/β-TCP and autogenous bone in a canine guided-bone regeneration model. Reviewed

Shuji Nosho, Mitsuaki Ono, Taishi Komori, Akihiro Mikai, Ikue Tosa, Kei Ishibashi, Yukie Tanaka, Aya Kimura-Ono, Emilio S Hara, Toshitaka Oohashi, Takuo Kuboki

Journal of prosthodontic research 66 ( 1 ) 124 - 130 2022.1

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

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

A retrospective comparison of the survival of vital teeth adjacent to single, bounded edentulous spaces rehabilitated using implant-supported, resin-bonded, and conventional fixed dental prostheses. Reviewed International journal

Shun Okuni, Kenji Maekawa, Takuya Mino, Yoko Kurosaki, Takuo Kuboki

Journal of dentistry 116 103911 - 103911 2022.1

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

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

Risk factors for root caries annual incidence and progression among older people requiring nursing care: A one-year prospective cohort study Reviewed

Kana Tokumoto, Aya Kimura-Ono, Takuya Mino, Suguru Osaka, Ken Numoto, Eri Koyama, Yoko Kurosaki, Shinsuke Nakagawa, Yuki Amano, Ha Thi Thu Nguyen, Takaharu Higuchi, Kumiko Nawachi, Mitsuaki Ono, Yoshitomo Kobayashi, Michiyo Yamamoto, Kenji Maekawa, Takuo Kuboki

Journal of Prosthodontic Research 66 ( 2 ) 250 - 257 2022.1

Suppression of Bone Necrosis around Tooth Extraction Socket in a MRONJ-like Mouse Model by E-rhBMP-2 Containing Artificial Bone Graft Administration. Reviewed International journal

Yukie Tanaka, Kyaw Thu Aung, Mitsuaki Ono, Akihiro Mikai, Anh Tuan Dang, Emilio Satoshi Hara, Ikue Tosa, Kei Ishibashi, Aya Ono-Kimura, Kumiko Nawachi, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 22 ( 23 ) 2021.11

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

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

Six-year follow-up assessment of prosthesis survival and oral health-related quality of life in individuals with partial edentulism treated with three types of prosthodontic rehabilitation. Reviewed

Yoko Kurosaki, Aya Kimura-Ono, Takuya Mino, Hikaru Arakawa, Eri Koyama, Shinsuke Nakagawa, Ha Thi Thu Nguyen, Suguru Osaka, Mamiko Saeki, Hajime Minakuchi, Mitsuaki Ono, Kenji Maekawa, Takuo Kuboki

Journal of prosthodontic research 65 ( 3 ) 332 - 339 2021.8

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

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴まで Step by Stepでわかる成功のポイント(完)(Step 6) 術後のメインテナンスのポイント Reviewed

岩田光弘, 窪木拓男

日本歯科評論 81 ( 6 ) 115 - 123 2021.6

A Road Map for Innovation to Drive Oral Implantology toward 2040:What Will Be Required in the Next 20 Years to Improve and Strengthen the JSOI? Reviewed

窪木拓男, 窪木拓男

日本口腔インプラント学会誌 34 ( 2 ) 115 - 123 2021.6

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴までStep by Stepでわかる成功のポイント(Step 5) 補綴手技のポイント(2)

岩田光弘, 山本桂輔, 窪木拓男

日本歯科評論 81 ( 5 ) 89 - 97 2021.5

認知機能低下、認知症と口腔顔面痛文献レビュー

前川賢治, 窪木拓男

日本口腔顔面痛学会雑誌 13 ( 1 ) 1 - 10 2021.5

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)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J05586&link_issn=&doc_id=20210604390001&doc_link_id=10.11264%2Fjjop.13.1&url=https%3A%2F%2Fdoi.org%2F10.11264%2Fjjop.13.1&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

岡山大学病院における放射線治療支援への取り組み

宮崎文伸, 松崎秀信, 松崎久美子, 青山英樹, 宇野弘文, 竹内哲男, 上田明広, 太田圭二, 浅海淳一, 窪木拓男

日本口腔顎顔面技工学会会誌 20 ( 1 ) 44 - 44 2021.4

食力向上による健康寿命の延伸:補綴歯科の意義補綴歯科治療は生命予後の延伸に貢献できるか?

窪木拓男, 前川賢治

日本補綴歯科学会誌 13 ( 2 ) 117 - 125 2021.4

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)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J05334&link_issn=&doc_id=20210428220004&doc_link_id=130008031302&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130008031302&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴までStep by Stepでわかる成功のポイント(Step 4) 補綴手技のポイント(1)

岩田光弘, 山本桂輔, 窪木拓男

日本歯科評論 81 ( 4 ) 103 - 110 2021.4

Newly developed data-matching methodology for oral implant surgery allowing the automatic deletion of metal artifacts in 3D-CT images using new reference markers: A case report.

Hiroaki Shimizu, Hikaru Arakawa, Takuya Mino, Yoko Kurosaki, Kana Tokumoto, Takuo Kuboki

Journal of prosthodontic research 65 ( 1 ) 125 - 129 2021.2

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

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

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴までStep by Stepでわかる成功のポイント(Step 3) 外科のポイント(2)

岩田光弘, 窪木拓男

日本歯科評論 81 ( 2 ) 131 - 140 2021.2

Tryptophan and Kynurenine Enhances the Stemness and Osteogenic Differentiation of Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro and In Vivo. International journal

Hai Thanh Pham, Mitsuaki Ono, Emilio Satoshi Hara, Ha Thi Thu Nguyen, Anh Tuan Dang, Hang Thuy Do, Taishi Komori, Ikue Tosa, Yuri Hazehara-Kunitomo, Yuya Yoshioka, Yasutaka Oida, Kentaro Akiyama, Takuo Kuboki

Materials (Basel, Switzerland) 14 ( 1 ) 208 - 208 2021.1

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

A comparison of colorimetric and visual methods for the assessment of masticatory performance with color-changeable chewing gum in older persons. International journal

Yoshihiro Kugimiya, Yutaka Watanabe, Maki Shirobe, Yoshiko Motohashi, Keiko Motokawa, Ayako Edahiro, Yuki Ohara, Masahiro Ryu, Kentaro Igarashi, Daichi Hoshino, Junko Nakajima, Takayuki Ueda, Yu Taniguchi, Toru Ogawa, Kenji Maekawa, Katsushi Tamaki, Takuo Kuboki, Akihiko Kitamura, Shoji Shinkai, Hirohiko Hirano

Journal of dental sciences 16 ( 1 ) 380 - 388 2021.1

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

Can prosthodontic treatment improve mortality in various life stages?

Takuo Kuboki, Kenji Maekawa

Annals of Japan Prosthodontic Society 13 ( 2 ) 117 - 125 2021

これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴まで Step by Stepでわかる成功のポイント(Step 2)外科のポイント(1)

岩田光弘, 窪木拓男

日本歯科評論 80 ( 12 ) 93 - 102 2020.12

IMPLANT THERAPY これで自信をもって取り組める前歯部インプラント治療診断から埋入、補綴までStep by Stepでわかる成功のポイント(Step 1) 診査・診断のポイント

岩田光弘, 窪木拓男

日本歯科評論 80 ( 11 ) 71 - 80 2020.11

Aging-Affected MSC Functions and Severity of Periodontal Tissue Destruction in a Ligature-Induced Mouse Periodontitis Model. International journal

Kyaw Thu Aung, Kentaro Akiyama, Masayoshi Kunitomo, Aung Ye Mun, Ikue Tosa, Ha Thi Thu Nguyen, Jiewen Zhang, Teisaku Kohno, Mitsuaki Ono, Emilio Satoshi Hara, Takuo Kuboki

International journal of molecular sciences 21 ( 21 ) 2020.10

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

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

Distinct Osteogenic Potentials of BMP-2 and FGF-2 in Extramedullary and Medullary Microenvironments. International journal

Shuji Nosho, Ikue Tosa, Mitsuaki Ono, Emilio Satoshi Hara, Kei Ishibashi, Akihiro Mikai, Yukie Tanaka, Aya Kimura-Ono, Taishi Komori, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 21 ( 21 ) 2020.10

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

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

【「高齢者の食べることを支援するIPE・IPWについて」】介護保険施設、在宅における多職種ミールラウンドや口腔栄養関連サービスをいかに根付かせるかミールラウンドとそれに基づくカンファレンスを多職種連携スモールグループディスカッション教育で模倣した試み

窪木拓男, 縄稚久美子, 水口真実, 前田あずさ, 中村幸伸, 日笠晴香, 佐川敬一朗, 田代晴基, 戸原雄, 高橋賢晃, 菊谷武

保健医療福祉連携 13 ( 2 ) 119 - 124 2020.10

BMP-2/β-TCP Local Delivery for Bone Regeneration in MRONJ-Like Mouse Model. International journal

Akihiro Mikai, Mitsuaki Ono, Ikue Tosa, Ha Thi Thu Nguyen, Emilio Satoshi Hara, Shuji Nosho, Aya Kimura-Ono, Kumiko Nawachi, Takeshi Takarada, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 21 ( 19 ) 2020.9

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

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

Safe and Predictable Hard Tissue Augmentation Modalities and Their Proper Use

小田師巳, 小田師巳, 園山亘, 園山亘, 窪木拓男

日本口腔インプラント学会誌 33 ( 3 ) 266 - 274 2020.9

AIによる医療革命に備える歯科界はAIの進歩にどのように対応するのか?

窪木拓男, 松岡由幸, 山口高平, 井汲憲治

The Quintessence 39 ( 7 ) 1666 - 1673 2020.7

Number of functional teeth more strongly predicts all-cause mortality than number of present teeth in Japanese older adults. Reviewed

Kenji Maekawa, Tomoko Ikeuchi, Shoji Shinkai, Hirohiko Hirano, Masahiro Ryu, Katsushi Tamaki, Hirofumi Yatani, Takuo Kuboki, Aya Kimura-Ono, Takeshi Kikutani, Takashi Suganuma, Yasunori Ayukawa, Tomoya Gonda, Toru Ogawa, Masanori Fujisawa, Shoichi Ishigaki, Yutaka Watanabe, Akihiko Kitamura, Yu Taniguchi, Yoshinori Fujiwara, Ayako Edahiro, Yuki Ohara, Junichi Furuya, Junko Nakajima, Kento Umeki, Kentaro Igarashi, Yasuhiro Horibe, Yoshihiro Kugimiya, Yasuhiko Kawai, Hideo Matsumura, Tetsuo Ichikawa, Shuji Ohkawa

Geriatrics & gerontology international 20 ( 6 ) 607 - 614 2020.6

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

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

A Re-evaluation of Implant Treatment Based on Causes of Missing Teeth : Implant Treatment for Patients Who Have Lost Teeth Due to Severe Periodontitis

岩田光弘, 荒川光, 中川晋輔, 窪木拓男

日本口腔インプラント学会誌 33 ( 2 ) 134 - 141 2020.6

Association of masticatory muscle activity with sleep arousal and other concomitant movements during sleep. Reviewed International journal

Haruna Miki, Hajime Minakuchi, Mayu Miyagi, Emilio Satoshi Hara, Shuji Shigemoto, Yoshitaka Suzuki, Kenji Maekawa, Yoshizo Matsuka, Glenn T Clark, Takuo Kuboki

Journal of oral rehabilitation 47 ( 3 ) 281 - 288 2020.3

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

Vibratory splint therapy for decreasing sleep clenching: A pilot study. Reviewed International journal

Emilio Satoshi Hara, Andrea Lusvarghi Witzel, Hajime Minakuchi, Carlos Eduardo de Pitta, Rosane Tronquin Gallo, Masahiro Okada, Takuya Matsumoto, Takuo Kuboki, Marcelo Costa Bolzan

Cranio : the journal of craniomandibular practice 38 ( 1 ) 15 - 21 2020.1

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

Full Digital Workflow for Use of a Scanbody to Accurately Transfer Morphology From Provisional to Final Implant-Supported Fixed Restoration. International journal

Takuya Mino, Yoko Kurosaki, Kenji Maekawa, Kana Tokumoto, Koji Izumi, Akihiro Ueda, Aya Kimura-Ono, Takuo Kuboki

The Journal of oral implantology 45 ( 6 ) 494 - 498 2019.12

Postnatal Runx2 deletion causes age-related changes in bone.

Ikue Tosa, Daisuke Yamada, Shunpei Tsukamoto, Kenji Kawabe, Takeshi Takarada, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki

JOURNAL OF BONE AND MINERAL RESEARCH 34 219 - 219 2019.12

Relationship between oral environment and development of pneumonia and acute viral respiratory infection in dependent older individuals.

Haruki Tashiro, Takeshi Kikutani, Fumiyo Tamura, Noriaki Takahashi, Takashi Tohara, Kumiko Nawachi, Kenji Maekawa, Takuo Kuboki

Geriatrics & gerontology international 19 ( 11 ) 1136 - 1140 2019.11

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

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

Secondary Publication 補綴歯科治療の難易度を測定するプロトコルの妥当性の検討 (公社)日本補綴歯科学会による多施設臨床研究

窪木拓男, 市川哲雄, 馬場一美, 藤澤政紀, 佐藤博信, 會田英紀, 小山重人, 秀島雅之, 佐藤裕二, 和気裕之, 大野彩, 木村, 永尾寛, 上田順加, 平, 玉置勝司, 貞森紳丞, 津賀一弘, 西恭宏, 澤瀬隆, 越野寿, 鱒見進一, 櫻井薫, 石橋寛二, 大山喬史, 赤川安正, 平井敏博, 佐々木啓一, 古谷野潔, 矢谷博文, 松村英雄

日本補綴歯科学会誌 11 ( 4 ) 355 - 375 2019.10

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

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

【二次出版】Secondary Publication 補綴歯科治療の難易度を測定するプロトコルの妥当性の検討 (公社)日本補綴歯科学会による多施設臨床研究

窪木拓男, 市川哲雄, 馬場一美, 藤澤政紀, 佐藤博信, 會田英紀, 小山重人, 秀島雅之, 佐藤裕二, 和気裕之, 大野彩[木村], 永尾寛, 上田順加[小平], 玉置勝司, 貞森紳丞, 津賀一弘, 西恭宏, 澤瀬隆, 越野寿, 鱒見進一, 櫻井薫, 石橋寛二, 大山喬史, 赤川安正, 平井敏博, 佐々木啓一, 古谷野潔, 矢谷博文, 松村英雄

日本補綴歯科学会誌 11 ( 4 ) 355 - 375 2019.10

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)

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

Type XVIII Collagen Modulates Keratohyalin Granule Formation and Keratinization in Oral Mucosa. Reviewed International journal

Ha Thi Thu Nguyen, Mitsuaki Ono, Emilio Satoshi Hara, Taishi Komori, Midori Edamatsu, Tomoko Yonezawa, Aya Kimura-Ono, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

International journal of molecular sciences 20 ( 19 ) 2019.9

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

Postnatal Runx2 deletion leads to low bone mass and adipocyte accumulation in mice bone tissues. Reviewed International journal

Ikue Tosa, Daisuke Yamada, Misa Yasumatsu, Eiichi Hinoi, Mitsuaki Ono, Toshitaka Oohashi, Takuo Kuboki, Takeshi Takarada

Biochemical and biophysical research communications 516 ( 4 ) 1229 - 1233 2019.9

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

Loss of oral self-care ability results in a higher risk of pneumonia in older inpatients: A prospective cohort study in a Japanese rural hospital. International journal

Aya Fujiwara, Hajime Minakuchi, Junji Uehara, Haruna Miki, Mami Inoue-Minakuchi, Aya Kimura-Ono, Kumiko Nawachi, Kenji Maekawa, Takuo Kuboki

Gerodontology 36 ( 3 ) 236 - 243 2019.9

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

Fibronectin-induced ductal formation in salivary gland self-organization model. International journal

Mahmoud Farahat, Gulsan A S Kazi, Hiroaki Taketa, Emilio S Hara, Masamitsu Oshima, Takuo Kuboki, Takuya Matsumoto

Developmental dynamics : an official publication of the American Association of Anatomists 248 ( 9 ) 813 - 825 2019.9

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

Fifteen-year survival of resin-bonded vs full-coverage fixed dental prostheses. Reviewed

T Yoshida, Y Kurosaki, A Mine, A Kimura-Ono, T Mino, S Osaka, S Nakagawa, K Maekawa, T Kuboki, H Yatani, A Yamashita

Journal of prosthodontic research 63 ( 3 ) 374 - 382 2019.7

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

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

Biomimetic mineralization using matrix vesicle nanofragments. Reviewed International journal

Yosuke Kunitomi, Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takuo Kuboki, Takayoshi Nakano, Hiroshi Kamioka, Takuya Matsumoto

Journal of biomedical materials research. Part A 107 ( 5 ) 1021 - 1030 2019.5

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

Acidic Pre-Conditioning Enhances the Stem Cell Phenotype of Human Bone Marrow Stem/Progenitor Cells. Reviewed International journal

Yuri Hazehara-Kunitomo, Emilio Satoshi Hara, Mitsuaki Ono, Kyaw Thu Aung, Keiko Komi, Hai Thanh Pham, Kentaro Akiyama, Masahiro Okada, Toshitaka Oohashi, Takuya Matsumoto, Takuo Kuboki

International journal of molecular sciences 20 ( 5 ) 2019.3

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

The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin. Reviewed

Hany Mohamed Khattab, Satoshi Kubota, Masaharu Takigawa, Takuo Kuboki, Walter Sebald

Journal of bone and mineral metabolism 37 ( 2 ) 199 - 205 2019.3

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

Bone Marrow Cells Inhibit BMP-2-Induced Osteoblast Activity in the Marrow Environment. International journal

Ha Thi Nguyen, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Thi Thu Nguyen, Kyaw Thu Aung, Hai Thanh Pham, Ikue Tosa, Takeshi Takarada, Koichi Matsuo, Toshihide Mizoguchi, Toshitaka Oohashi, Takuo Kuboki

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 34 ( 2 ) 327 - 332 2019.2

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

Digital transfer of the subgingival contour and emergence profile of the provisional restoration to the final bone-anchored fixed restoration. Reviewed

Yoko Kurosaki, Takuya Mino, Kenji Maekawa, Koji Izumi, Takuo Kuboki

Journal of prosthodontic research 63 ( 1 ) 125 - 129 2019.1

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

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

DNA Methylation-Based Regulation of Human Bone Marrow-Derived Mesenchymal Stem/Progenitor Cell Chondrogenic Differentiation. Reviewed International journal

Yu Nomura, Emilio Satoshi Hara, Yuya Yoshioka, Há Thi Nguyen, Shuji Nosho, Taishi Komori, Kei Ishibashi, Toshitaka Oohashi, Mitsuaki Ono, Takuo Kuboki

Cells, tissues, organs 207 ( 3-4 ) 115 - 126 2019

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

Novel function of BMP-2 in inhibiting bone formation in marrow environment

Ha Nguyen Thi, Mitsuaki Ono, Yasutaka Oida, Emilio Satoshi Hara, Taishi Komori, Kentaro Akiyama, Ha Nguyen Thi Thu, Hai Thanh Pham, Kyawthu Aung, Toshitaka Oohashi, Takuo Kuboki

JOURNAL OF BONE AND MINERAL RESEARCH 33 338 - 338 2018.11

Rapid bioinspired mineralization using cell membrane nanofragments and alkaline milieu. Reviewed International journal

Emilio Satoshi Hara, Masahiro Okada, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

Journal of materials chemistry. B 6 ( 38 ) 6153 - 6161 2018.10

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

日本人を対象とした過去20年間の口腔インプラント治療の臨床成績に関するシステマティックレビュー

三野卓哉, 小田師巳, 園山亘, 窪木拓男

Quintessence Dental Implantology 25 ( 5 ) 0746‐0757 - 0757 2018.9

CCN4/WISP1 controls cutaneous wound healing by modulating proliferation, migration and ECM expression in dermal fibroblasts via α5β1 and TNFα. International journal

Mitsuaki Ono, Asuka Masaki, Azusa Maeda, Tina M Kilts, Emilio S Hara, Taishi Komori, Hai Pham, Takuo Kuboki, Marian F Young

Matrix biology : journal of the International Society for Matrix Biology 68-69 533 - 546 2018.8

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

多職種連携教育の導入・充実を目指して全国29歯科大学、歯学部多職種連携教育アンケート集計結果 Reviewed

片岡竜太, 浅沼直樹, 窪木拓男, 越野寿, 澤瀬隆, 角忠輝, 筒井睦

日本歯科医学教育学会総会・学術大会プログラム・抄録集 37回 76 - 76 2018.7

The BMP-2 mutant L51P: a BMP receptor IA binding-deficient inhibitor of noggin Reviewed

Hany Mohamed Khattab, Satoshi Kubota, Masaharu Takigawa, Takuo Kuboki, Walter Sebald

JOURNAL OF BONE AND MINERAL METABOLISM 128 ( 3 ) 181 - 196 2018.4

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

A multi-centered epidemiological study evaluating the validity of the treatment difficulty indices developed by the Japan Prosthodontic Society. Reviewed

Takuo Kuboki, Tetsuo Ichikawa, Kazuyoshi Baba, Masanori Fujisawa, Hironobu Sato, Hideki Aita, Shigeto Koyama, Masayuki Hideshima, Yuji Sato, Hiroyuki Wake, Aya Kimura-Ono, Kan Nagao, Yorika Kodaira-Ueda, Katsushi Tamaki, Shinsuke Sadamori, Kazuhiro Tsuga, Yasuhiro Nishi, Takashi Sawase, Hisashi Koshino, Shin-Ichi Masumi, Kaoru Sakurai, Kanji Ishibashi, Takashi Ohyama, Yasumasa Akagawa, Toshihiro Hirai, Keiichi Sasaki, Kiyoshi Koyano, Hirofumi Yatani, Hideo Matsumura

Journal of prosthodontic research 62 ( 2 ) 162 - 170 2018.4

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

Type IV collagen α6 chain is a regulator of keratin 10 in keratinization of oral mucosal epithelium. International journal

Taishi Komori, Mitsuaki Ono, Emilio Satoshi Hara, Junji Ueda, Ha Thi Thu Nguyen, Ha Thi Nguyen, Tomoko Yonezawa, Takahiro Maeba, Aya Kimura-Ono, Takeshi Takarada, Ryusuke Momota, Kenji Maekawa, Takuo Kuboki, Toshitaka Oohashi

Scientific reports 8 ( 1 ) 2612 - 2612 2018.2

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

Chondrocyte burst promotes space for mineral expansion. Reviewed International journal

Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Letycia Mary Iida, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

Integrative biology : quantitative biosciences from nano to macro 10 ( 1 ) 57 - 66 2018.1

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

Bioinspired Mineralization Using Chondrocyte Membrane Nanofragments. Reviewed International journal

Emilio Satoshi Hara, Masahiro Okada, Noriyuki Nagaoka, Takako Hattori, Takuo Kuboki, Takayoshi Nakano, Takuya Matsumoto

ACS biomaterials science & engineering 4 ( 2 ) 617 - 625 2018.1

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

Practical whole-tooth restoration utilizing autologous bioengineered tooth germ transplantation in a postnatal canine model. International journal

Mitsuaki Ono, Masamitsu Oshima, Miho Ogawa, Wataru Sonoyama, Emilio Satoshi Hara, Yasutaka Oida, Shigehiko Shinkawa, Ryu Nakajima, Atsushi Mine, Satoru Hayano, Satoshi Fukumoto, Shohei Kasugai, Akira Yamaguchi, Takashi Tsuji, Takuo Kuboki

Scientific reports 7 44522 - 44522 2017.3

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

Oral Rehabilitation utilizing Several Types of Overdentures

Masumi Shin-ichi, Kuboki Takuo

Annals of Japan Prosthodontic Society 9 ( 4 ) 303 - 303 2017

地域包括ケアの多職種協働の中で, 今まさに『歯科医師』が果たすべき役割は？

片岡竜太, 飯島勝矢, 早坂由美子, 松井由美子, 杉山みち子, 窪木拓男

日本歯科医学教育学会雑誌 33 ( 3 ) 149 - 151 2017

矯正歯科治療前および治療済の患者における口腔関連Quality of Lifeと各種歯科矯正学的指標の関連性

加藤ゆい, 川邉紀章, 古森紘基, 片岡伴記, 藤澤厚郎, 大野彩, 窪木拓男, 山城隆, 上岡寛

日本矯正歯科学会大会プログラム・抄録集 75回 226 - 226 2016.11

Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug Reviewed

Abdelkader Tarek, Aoyama Eriko, Nishida Takashi, Hattori Takako, Janune Danilo, Hara Emilio S, Ono Mitsuaki, Tabata Yasuhiko, Kuboki Takuo, Kubota Satoshi, Takigawa Masaharu

FASEB JOURNAL 30 2016.4

Assessment of CCN2 Independent Modules Regenerative Capacity on Osteoarthritis and Further Selecting the Most Suitable Among them as a Potential Therapeutic Drug Reviewed

Abdelkader Tarek, Aoyama Eriko, Nishida Takashi, Hattori Takako, Janune Danilo, Hara Emilio S, Ono Mitsuaki, Tabata Yasuhiko, Kuboki Takuo, Kubota Satoshi, Takigawa Masaharu

FASEB JOURNAL 30 2016.4

Highly dynamic self-organizing SMG morphogenesis in 3D culture Reviewed

Mahmoud Farahat, Gulsan Ara Sathi, Hiroaki Taketa, Masamitsu Oshima, Takuo Kuboki, Takuya Matsumoto

2015 International Symposium on Micro-NanoMechatronics and Human Science, MHS 2015 2016.3

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

Cellular Reprogramming Using Defined Factors and MicroRNAs International journal

Takanori Eguchi, Takuo Kuboki

STEM CELLS INTERNATIONAL 2016 ( 2016 ) 1 - 12 2016

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

Changes in joint space dimension after the correction of Class II division 1 malocclusion. International journal

Alberto Cacho, Tsuyoshi Ono, Takuo Kuboki, Conchita Martin

European journal of orthodontics 37 ( 5 ) 467 - 73 2015.10

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

Concealed Jiggling Effect: A Novel Risk Factor for Complications of Implant-Supported Fixed Partial Denture. International journal

Ryu Nakajima, Kenji Maekawa, Wataru Sonoyama, Akihiro Ueda, Takuo Kuboki

The Journal of oral implantology 41 ( 4 ) 491 - 4 2015.8

A risk factor analysis of accumulated postoperative pain and swelling sensation after dental implant surgery using a cellular phone-based real-time assessment.

Ryuta Kuroi, Hajime Minakuchi, Emilio Satoshi Hara, Aya Kawakami, Kenji Maekawa, Hiroki Okada, Takuo Kuboki

Journal of prosthodontic research 59 ( 3 ) 194 - 8 2015.7

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

平成26年度にODAPUSプログラムで岡山大学に留学をした3ヶ国4校の学生の意識調査

藤田麻里子, 此内浩信, 柳文修, 久富美紀, 村上純, 窪木拓男, 宮脇卓也, 仲野道代, 浅海淳一

日本歯科医学教育学会総会・学術大会プログラム・抄録集 34回 143 - 143 2015.7

Peptide-modified Substrate for Modulating Gland Tissue Growth and Morphology In Vitro. International journal

Hiroaki Taketa, Gulsan Ara Sathi, Mahmoud Farahat, Kazi Anisur Rahman, Takayoshi Sakai, Yoshiaki Hirano, Takuo Kuboki, Yasuhiro Torii, Takuya Matsumoto

Scientific reports 5 11468 - 11468 2015.6

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

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

Interdisciplinary orthodontic treatment for a patient with generalized aggressive periodontitis: Assessment of IgG antibodies to identify type of periodontitis and correct timing of treatment. International journal

Yoshihito Ishihara, Kazuya Tomikawa, Toru Deguchi, Tadashi Honjo, Koji Suzuki, Takayuki Kono, Takuo Kuboki, Hiroshi Kamioka, Shogo Takashiba, Takashi Yamashiro

American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics 147 ( 6 ) 766 - 80 2015.6

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

健常者における睡眠時の覚醒反応と随伴運動との関連

三木春奈, 水口一, 上枝麻友, 重本修伺, 鈴木善貴, 前川賢治, 松香芳三, 窪木拓男

日本補綴歯科学会誌 7 ( 特別号 ) 248 - 248 2015.5

In silico comparison of the reproducibility of full-arch implant provisional restorations to final restoration between a 3D Scan/CAD/CAM technique and the conventional method.

Takuya Mino, Kenji Maekawa, Akihiro Ueda, Shizuo Higuchi, Junichi Sejima, Tetsuo Takeuchi, Emilio Satoshi Hara, Aya Kimura-Ono, Wataru Sonoyama, Takuo Kuboki

Journal of prosthodontic research 59 ( 2 ) 152 - 8 2015.4

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

咬合違和感を訴える患者の実態に関する多施設実態調査 Reviewed

澁谷智明, 和気裕之, 玉置勝司, 島田淳, 古谷野潔, 鱒見進一, 窪木拓男, 皆木省吾, 貞森紳丞, 矢谷博文, 藤澤政紀, 林勝彦, 玉井和樹, 成田紀之, 原節宏, 馬場一美, 尾口仁志, 金村清孝, 山口泰彦, 西川洋二, 塚原宏泰, 松香芳三, 葉山莉香

日顎誌 26 ( 3 ) 196 - 203 2015.2

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

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

The Effect of Tooth Loss and/or Oral Function to Nutritional Status -Assessment of These Relationship

Takeshi KIKUTANI, Mitsuyoshi YOSHIDA, Takeo SUGA, Toshihide KIMURA, Fumiyo TAMURA, Takuo KUBOKI

日本歯科医学会誌 34 59 - 63 2015

Food Ingestion/Mastication/Swallowing Evaluation Method Corre- sponding to the Stage of Patients and Its Application: Feasibility of an Oral Function Test

Mami INOUE-MINAKUCHI, Kenji MAEKAWA, Takeshi KIKUTANI, Fumiyo TAMURA, Mitsuyoshi YOSHIDA, Tomohisa ONO, Yasushi TAMADA, Hisatomo KONDO, Katsuhiko KIMOTO, Shuji OHKAWA, Yuji SATO, Hiroshi SUZUKI, Misao KAWARA, Takuo KUBOKI

34 94 - 98 2015

Topical application of lithium chloride on the pulp induces dentin regeneration. International journal

Kazuya Ishimoto, Satoru Hayano, Takeshi Yanagita, Hiroshi Kurosaka, Noriaki Kawanabe, Shinsuke Itoh, Mitsuaki Ono, Takuo Kuboki, Hiroshi Kamioka, Takashi Yamashiro

PloS one 10 ( 3 ) e0121938 2015

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

Establishment of Valid Diagnosis Methods and the Management for Sleep Bruxism Reviewed

大倉一夫, 大川周治, 藤澤政紀, 櫻井薫, 馬場一美, 小川匠, 矢谷博文, 窪木拓男, 松香芳三

日本歯科医学会誌 34 79 - 83 2015

OstemiR: A Novel Panel of MicroRNA Biomarkers in Osteoblastic and Osteocytic Differentiation from Mesencymal Stem Cells Reviewed

Eguchi, Takanori, Hara, Emilio Satoshi, Ono, Mitsuaki, Watanabe, Ken, Kuboki, Takuo, Calderwood, Stuart

Faseb Journal 29 2015

The BMP2 antagonist inhibitor L51P enhances the osteogenic potential of BMP2 by simultaneous and delayed synergism. International journal

Hany Mohamed Khattab, Mitsuaki Ono, Wataru Sonoyama, Yasutaka Oida, Shigehiko Shinkawa, Yuya Yoshioka, Kenji Maekawa, Yasuhiko Tabata, Kazushige Sugama, Walter Sebald, Takuo Kuboki

Bone 69 165 - 73 2014.12

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

Comparison of platelet serotonin transporter activity in subjects with severe sleep bruxism and control.

Hajime Minakuchi, Chiharu Sogawa, Emilio Satoshi Hara, Haruna Miki, Kenji Maekawa, Norio Sogawa, Shigeo Kitayama, Yoshizo Matsuka, Glenn T Clark, Takuo Kuboki

Journal of prosthodontic research 58 ( 4 ) 217 - 22 2014.10

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

Dentin-smear remains at self-etch adhesive interface. International journal

Atsushi Mine, Jan De Munck, Marcio Vivan Cardoso, Kirsten L Van Landuyt, André Poitevin, Annelies Van Ende, Mariko Matsumoto, Yasuhiro Yoshida, Takuo Kuboki, Hirofumi Yatani, Bart Van Meerbeek

Dental materials : official publication of the Academy of Dental Materials 30 ( 10 ) 1147 - 53 2014.10

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

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy. International journal

Masamitsu Oshima, Kaoru Inoue, Kei Nakajima, Tetsuhiko Tachikawa, Hiromichi Yamazaki, Tomohide Isobe, Ayaka Sugawara, Miho Ogawa, Chie Tanaka, Masahiro Saito, Shohei Kasugai, Teruko Takano-Yamamoto, Takashi Inoue, Katsunari Tezuka, Takuo Kuboki, Akira Yamaguchi, Takashi Tsuji

Scientific reports 4 6044 - 6044 2014.8

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

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

簡易貼付型睡眠時ブラキシズム測定装置の測定精度の検討

三木春奈, 水口一, 上枝麻友, 重本修伺, 鈴木善貴, 前川賢治, 松香芳三, 窪木拓男

日本顎関節学会雑誌 26 ( Suppl. ) 125 - 125 2014.7

Direct interaction between CCN family protein 2 and fibroblast growth factor 1. International journal

Tarek Abd El Kader, Satoshi Kubota, Ken Anno, Saho Tanaka, Takashi Nishida, Takayuki Furumatsu, Eriko Aoyama, Takuo Kuboki, Masaharu Takigawa

Journal of cell communication and signaling 8 ( 2 ) 157 - 63 2014.6

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

A short-term treatment with tumor necrosis factor-alpha enhances stem cell phenotype of human dental pulp cells. International journal

Mayu Ueda, Takuo Fujisawa, Mitsuaki Ono, Emilio Satoshi Hara, Hai Thanh Pham, Ryu Nakajima, Wataru Sonoyama, Takuo Kuboki

Stem cell research & therapy 5 ( 1 ) 31 - 31 2014.2

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

Mesenchymal Stem/Progenitor Cell Isolation from Tooth Extraction Sockets

Nakajima, R., Ono, M., Hara, E. S., Oida, Y., Shinkawa, S., Pham, H. T., Akiyama, K., Sonoyama, W., Maekawa, K., Kuboki, T.

Journal of Dental Research 93 ( 11 ) 1133 - 1140 2014

Efficient bone formation in swine socket-lift model using E. coli-derived rhBMP-2 adsorbed in b-TCP.

Ono M, Sonoyama W, Yamamoto K, Oida Y, Akiyama K, Shinkawa S, Nakajima R, Pham HT, Hara ES, Kuboki T

199 ( 4 ) 249 - 255 2014

Efficient bone formation in a swine socket lift model using Escherichia coli-derived recombinant human bone morphogenetic protein-2 adsorbed in β-tricalcium phosphate. Reviewed International journal

Mitsuaki Ono, Wataru Sonoyama, Katushi Yamamoto, Yasutaka Oida, Kentaro Akiyama, Shigehiko Shinkawa, Ryu Nakajima, Hai T Pham, Emilio S Hara, Takuo Kuboki

Cells, tissues, organs 199 ( 4 ) 249 - 55 2014

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

Immunotherapy in Transplantation Reviewed

Akiyama, K., Hara Satoshi, E., Kuboki, T.

Stem Cell Biology and Tissue Engineering in Dental Sciences 831 2014

miRNA-720 regulates the stem cell phenotype and differentiation of human dental pulp-derived mesenchymal stromal cells Reviewed

Hara, Emilio Satoshi, Ono, Mitsuaki, Eguchi, Takanori, Hai Thanh Pham, Tajima, Shoji, Calderwood, Stuart K., Matsumoto, Takuya, Kuboki, Takuo, IEEE

2014 International Symposium on Micro-Nanomechatronics and Human Science (Mhs) 2014

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

Clinical Applications of Computerized Bone Models Made by 3D Plaster Printing

吉本彰夫, 吉本彰夫, 十河基文, 荒川光, 植村修作, 窪木拓男

日本口腔インプラント学会誌 26 ( 4 ) 723 - 730 2013.12

Hydrolytic stability of three-step etch-and-rinse adhesives in occlusal class-I cavities. Reviewed International journal

Jan De Munck, Atsushi Mine, Marcio Vivan Cardoso, Kirsten L Van Landuyt, Anne-Katrin Lührs, André Poitevin, Masao Hanabusa, Takuo Kuboki, Bart Van Meerbeek

Clinical oral investigations 17 ( 8 ) 1911 - 8 2013.11

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

Reliability and validity of diagnostic nomenclature system of prosthetic dentistry Reviewed

松香芳三, 松香芳三, 萩原芳幸, 萩原芳幸, 玉置勝司, 玉置勝司, 竹内久裕, 藤澤政紀, 藤澤政紀, 小野高裕, 小野高裕, 築山能大, 永尾寛, 津賀一弘, 會田英紀, 會田英紀, 近藤尚知, 近藤尚知, 笛木賢治, 笛木賢治, 塚崎弘明, 塚崎弘明, 石橋寛二, 藤井重壽, 平井敏博, 佐々木啓一, 矢谷博文, 五十嵐順正, 佐藤裕二, 市川哲雄, 松村英雄, 山森徹雄, 窪木拓男, 馬場一美, 馬場一美, 古谷野潔

日本補綴歯科学会誌 5 ( 3 ) 281 - 290 2013.11

Regulation of CCN2 gene expression and possible roles in developing tooth germs. Reviewed International journal

Manabu Kanyama, Tsuyoshi Shimo, Hiroki Sugito, Motohiko Nagayama, Takuo Kuboki, Maurizio Pacifici, Eiki Koyama

Archives of oral biology 58 ( 11 ) 1659 - 66 2013.11

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

矯正歯科治療終了時の口腔関連Quality of Life評価

川邉紀章, 古森紘基, 片岡伴記, 白賀のり子, 大野彩, 窪木拓男, 山城隆

日本矯正歯科学会大会プログラム・抄録集 72回 223 - 223 2013.10

CCNファミリー遺伝子の発現プロフィールの操作を介したCCN3の線維化抑制作用の理解(Understanding the anti-fibrotic role of CCN3 through manipulation of CCN family gene expression profile)

El Kader Tarek Abd, Kubota Satoshi, Janune Danilo, Nishida Takashi, Hattori Takako, Aoyama Eriko, Perbal Bernard, Kuboki Takuo, Takigawa Masaharu

日本生化学会大会プログラム・講演要旨集 86回 1T11a - 15 2013.9

矯正歯科治療終了時の口腔関連Quality of Life評価

川邉紀章, 古森紘基, 片岡伴記, 白賀のり子, 大野彩, 窪木拓男, 山城隆

中・四国矯正歯科学会雑誌 25 ( 1 ) 70 - 70 2013.8

固定性架工義歯学技工実習での視覚教材としての動画配信システム Reviewed

中島隆, 水口一, 新川重彦, 瀧内博也, 正木明日香, 三野卓哉, 笈田育尚, 木村彩, 前川賢治, 窪木拓男

岡山歯学会雑誌 32 ( 1 ) 17 - 23 2013.6

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。

Anti-fibrotic effect of CCN3 accompanied by altered gene expression profile of the CCN family. Reviewed International journal

Tarek Abd El Kader, Satoshi Kubota, Danilo Janune, Takashi Nishida, Takako Hattori, Eriko Aoyama, Bernard Perbal, Takuo Kuboki, Masaharu Takigawa

Journal of cell communication and signaling 7 ( 1 ) 11 - 8 2013.3

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

Novel chondrogenic and chondroprotective effects of the natural compound harmine. Reviewed International journal

Emilio Satoshi Hara, Mitsuaki Ono, Satoshi Kubota, Wataru Sonoyama, Yasutaka Oida, Takako Hattori, Takashi Nishida, Takayuki Furumatsu, Toshifumi Ozaki, Masaharu Takigawa, Takuo Kuboki

Biochimie 95 ( 2 ) 374 - 81 2013.2

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

Regeneration of calvarial defects with Escherichia coli -derived rhBMP-2 adsorbed in PLGA membrane. Reviewed International journal

Mitsuaki Ono, Wataru Sonoyama, Kazuki Nema, Emilio Satoshi Hara, Yasutaka Oida, Hai Thanh Pham, Katushi Yamamoto, Kazuo Hirota, Kazushige Sugama, Walter Sebald, Takuo Kuboki

Cells, tissues, organs 198 ( 5 ) 367 - 76 2013

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

The CCN2-inducer harmine promotes chondrogenesis and protects against TNFα-induced ablation of chondrocytic phenotype Reviewed

Hara, E.S, M. Ono, S. Kubota, W. Sonoyama, Y. Oida, T. Hattori, T. Nishida, T. Furumatsu, T. Ozaki, M. Takigawa, T. Kuboki

Biochimie 95 374 - 381 2013

A problem-based learning tutorial for dental students regarding elderly residents in a nursing home in Japan. Reviewed International journal

Yoshizo Matsuka, Ryu Nakajima, Haruna Miki, Aya Kimura, Manabu Kanyama, Hajime Minakuchi, Shigehiko Shinkawa, Hiroya Takiuchi, Kumiko Nawachi, Kenji Maekawa, Hikaru Arakawa, Takuo Fujisawa, Wataru Sonoyama, Atsushi Mine, Emilio Satoshi Hara, Takeshi Kikutani, Takuo Kuboki

Journal of dental education 76 ( 12 ) 1580 - 8 2012.12

Language：English Publishing type：Research paper (scientific journal) Publisher：12

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.

Multiple sleep bruxism data collected using a self-contained EMG detector/analyzer system in asymptomatic healthy subjects. Reviewed International journal

Hajime Minakuchi, Chiyomi Sakaguchi, Emilio S Hara, Kenji Maekawa, Yoshizo Matsuka, Glenn T Clark, Takuo Kuboki

Sleep & breathing = Schlaf & Atmung 16 ( 4 ) 1069 - 72 2012.12

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

Multiple sleep bruxism data collected using a self-contained EMG detector/analyzer system in asymptomatic healthy subjects Reviewed International journal

Hajime Minakuchi, Chiyomi Sakaguchi, Emilio S. Hara, Kenji Maekawa, Yoshizo Matsuka, Glenn T. Clark, Takuo Kuboki

SLEEP AND BREATHING 16 ( 4 ) 1069 - 1072 2012.12

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

CCN2非依存性モジュールの軟骨再生能力(Cartilage regeneration potential of CCN2 independent modules)

El Kader Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

日本再生歯科医学会誌 10 ( 1 ) 50 - 50 2012.12

A prosthodontic medicine with collaboration between medical and dental sciences. Reviewed

Takuo Kuboki

Journal of prosthodontic research 56 ( 4 ) 227 - 8 2012.10

Matrix metalloproteinase-8 is the major potential collagenase in active peri-implantitis. Reviewed

Hikaru Arakawa, Junji Uehara, Emilio Satoshi Hara, Wataru Sonoyama, Aya Kimura, Manabu Kanyama, Yoshizo Matsuka, Takuo Kuboki

Journal of prosthodontic research 56 ( 4 ) 249 - 55 2012.10

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

Matrix metalloproteinase-8 is the major potential collagenase in active peri-implantitis Reviewed

Hikaru Arakawa, Junji Uehara, Emilio Satoshi Hara, Wataru Sonoyama, Aya Kimura, Manabu Kanyama, Yoshizo Matsuka, Takuo Kuboki

JOURNAL OF PROSTHODONTIC RESEARCH 56 ( 4 ) 249 - 255 2012.10

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 > 0.6 mm were included in the severe peri-implantitis group, and randomly selected, age-, gender- and implantation site-matched healthy patients (AVBL <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

歯科矯正治療を受診する患者の口腔関連Quality of Lifeの評価

古森紘基, 川邉紀章, 片岡伴記, 白賀のり子, 大野彩, 窪木拓男, 山城隆

日本矯正歯科学会大会プログラム・抄録集 71回 198 - 198 2012.9

矯正歯科治療患者の口腔関連Quality of Lifeの評価

古森紘基, 川邉紀章, 片岡伴記, 白賀のり子, 大野彩, 窪木拓男, 山城隆

中・四国矯正歯科学会雑誌 24 ( 1 ) 106 - 106 2012.8

Identification of novel transcription-regulating genes expressed during murine molar development. Reviewed International journal

Kenta Uchibe, Hirohito Shimizu, Shigetoshi Yokoyama, Takuo Kuboki, Hiroshi Asahara

Developmental dynamics : an official publication of the American Association of Anatomists 241 ( 7 ) 1217 - 26 2012.7

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

軟骨細胞と骨芽細胞に対するCCN2独立モジュールの影響(Effects of CCN2 independent modules on chondrocytic and osteoblastic cells)

El Kader Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

日本骨代謝学会学術集会プログラム抄録集 30回 232 - 232 2012.7

Bonding effectiveness of a new 'multi-mode' adhesive to enamel and dentine. Reviewed International journal

Masao Hanabusa, Atsushi Mine, Takuo Kuboki, Yasuko Momoi, Annelies Van Ende, Bart Van Meerbeek, Jan De Munck

Journal of dentistry 40 ( 6 ) 475 - 84 2012.6

Language：English Publishing type：Research paper (scientific journal) Publisher：6

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

Videoendoscopic assessment of swallowing function to predict the future incidence of pneumonia of the elderly Reviewed

N. Takahashi, T. Kikutani, F. Tamura, M. Groher, T. Kuboki

Journal of Oral Rehabilitation 39 ( 6 ) 429 - 437 2012.6

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

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

施設に入所している要介護高齢者の問題点を抽出するテュートリアル演習 Reviewed

松香芳三, 縄稚久美子, 中島隆, 三木春奈, 木村彩, 完山学, 水口一, 新川重彦, 瀧内博也, 前川賢治, 荒川光, 藤澤拓生, 園山亘, 峯篤史, 菊谷武, 窪木拓男

日本補綴歯科学会誌 4 ( 特別号 ) 279 - 279 2012.5

Stage-specific embryonic antigen-4 identifies human dental pulp stem cells. Reviewed International journal

Noriaki Kawanabe, Satoko Murata, Hiroaki Fukushima, Yoshihito Ishihara, Takeshi Yanagita, Emmy Yanagita, Mitsuaki Ono, Hiroshi Kurosaka, Hiroshi Kamioka, Tomoo Itoh, Takuo Kuboki, Takashi Yamashiro

Experimental cell research 318 ( 5 ) 453 - 63 2012.3

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

Influence of resin coating materials on Porphyromonas gingivalis attachment. Reviewed

Ai Kumada, Yoshizo Matsuka, Atsushi Mine, Mitsuaki Ono, Junji Uehara, Norihiro Sonoi, Takashi Ito, Shogo Takashiba, Takuo Kuboki

Dental materials journal 31 ( 1 ) 86 - 91 2012.2

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

Effect of low-shrinking composite on the bonding effectiveness of two adhesives in occlusal Class-I cavities.

Atsushi Mine, Jan De Munck, Marcio V Cardoso, Kirsten L Van Landuyt, André Poitevin, Takuo Kuboki, Yasuhiro Yoshida, Kazuomi Suzuki, Bart Van Meerbeek

Dental materials journal 31 ( 3 ) 418 - 26 2012

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

Intradermal injection of Botulinum toxin type A alleviates infraorbital nerve constriction-induced thermal hyperalgesia in an operant assay Reviewed

Kumada A, Matsuka Y, Spigelman I, Maruhama K, Yamamoto Y, Neubert J.K, Nolan T.A, Watanabe K, Maekawa K, Kamioka H, Yamashiro T, Kuboki T, Oguma K

Journal of Oral Rehabilitation 39 ( 1 ) 63 - 72 2012

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

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

Application of purified botulinum type a neurotoxin to treat experimental trigeminal neuropathy in rats and patients with urinary incontinence and prostatic hyperplasia. Reviewed International journal

Yoshizo Matsuka, Teruhiko Yokoyama, Yumiko Yamamoto, Tomonori Suzuki, Ni Nengah Dwi Fatmawati, Atsushi Nishikawa, Tohru Ohyama, Toshihiro Watanabe, Takuo Kuboki, Atsushi Nagai, Keiji Oguma

Journal of toxicology 2012 648384 - 648384 2012

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

Occlusal dysesthesia: a qualitative systematic review of the epidemiology, aetiology and management Reviewed

Hara, E. S., Matsuka, Y., Minakuchi, H., Clark, G. T., Kuboki, T.

Journal of Oral Rehabilitation 39 ( 8 ) 630 - 638 2012

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

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

Response shift in oral health-related quality of life measurement in patients with partial edentulism Reviewed

Kimura, A., Arakawa, H., Noda, K., Yamazaki, S., Hara, E. S., Mino, T., Matsuka, Y., Mulligan, R., Kuboki, T.

Journal of Oral Rehabilitation 39 ( 1 ) 44 - 54 2012

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

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 < 0・01), number of replaced teeth (fewer) (P < 0・01) and pre-test scores (lower) (P < 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

The association between oral health-related quality of life and self-rated presenteeism Reviewed

Takiuchi, Hiroya, Kimura-Ono, Aya, Arakawa, Hikaru, Mino, Takuya, Masaki, Asuka, Hara, Emilio Satoshi, Kanyama, Manabu, Matsuka, Yoshizo, Kuboki, Takuo

Quality of Life Research 21 71 - 72 2012

A problem-based learning tutorial on elder inpatients in a nursing home in Japan. Reviewed

Matsuka Y, Nakajima R, Miki H, Kimura A, Kanyama M, Minakuchi H, Shinkawa S, Takiuchi H, Nawachi K, Maekawa K, Arakawa H, Fujisawa T, Sonoyama W, Mine A, Hara ES, Kikutani T, Kuboki T

Journal of Dental Education 2012

軟骨細胞に対する、CCN2モジュールの単独・結合下での影響に関する評価(Evaluation of independent and combinational effect of CCN2 modules on chondorocytic cells)

El Kdaer Tarek Abd, Kubota Satoshi, Nishida Takashi, Hattori Takako, Aoyama Eriko, Janune Danilo, Kuboki Takuo, Takigawa Masaharu

日本骨代謝学会学術集会プログラム抄録集 29回 248 - 248 2011.7

CCN2/CTGF誘導因子であるハルミンは軟骨形成を促進し、TNF-α誘発炎症反応を抑制する(HARMINE, AN INDUCER OF CCN2/CTGF, PROMOTES CHONDROGENESIS AND SUPPRESSES TNF-α-INDUCED INFLAMMATORY RESPONSE)

Hara Emilio S.i, Ono Mitsuaki, Kubota Satoshi, Sonoyama Wataru, Hattori Takako, Takigawa Masaharu, Kuboki Takuo

日本骨代謝学会学術集会プログラム抄録集 29回 232 - 232 2011.7

RELATIONSHIP BETWEEN SLEEP BRUXISM FREQUENCY AND UPTAKE ABILITY OF HUMAN PERIPHERAL SEROTONIN TRANSPORTER Reviewed

Minakuchi, H., Hara, E. S., Sogawa, C., Miki, H., Fujisawa, T., Maekawa, K., Matsuka, Y., Sogawa, N., Kitayama, S., Kuboki, T.

Sleep 34 A201 - A202 2011

Peripheral administration of botulinum toxin type A neurotoxin reverses trigeminal neuropathic pain symptoms Reviewed

Ai Kumada, Yoshizo Matsuka, Igor Spigelman, John K Neubert, Todd A Nolan, Yumiko Yamamoto, Keiko Sato, Kazuhiro Watanabe, Takuo Kuboki, Keiji Oguma

http://f1000.com/posters/browse/summary/763 2011

The relationship between temporomandibular joint pathosis and muscle tenderness in the orofacial and neck/shoulder region. Reviewed

Eitoku Inoue, Kenji Maekawa, Hajime Minakuchi, Chiyomi Nagamatsu-Sakaguchi, Tsuyoshi Ono, Yoshizo Matsuka, GT Clark, Takuo Kuboki

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics Vol.109 ( No.1 ) 86 - 90 2010.1

周術期管理センター(歯科部門)のニーズと現況について経口気管挿管時に起こる歯の損傷とその対応

縄稚久美子, 山中玲子, 曽我賢彦, 柳文修, 兒玉直紀, 中田貴, 森田学, 窪木拓男, 足羽孝子, 森田潔

日本集中治療医学会雑誌 17 ( Suppl. ) 374 - 374 2010.1

顎関節症の診療ガイドラインに関するプロジェクト研究—スプリント治療ガイドラインの確立—． Reviewed

皆木省吾, 築山能大, 有馬太郎, 市川哲雄, 窪木拓男, 兒玉直紀, 佐久間重光, 新谷明喜, 高津匡樹, 竹内哲男, 津賀一弘, 坪井明人, 中島啓一朗, 中野雅徳, 成田紀之, 波多野泰夫, 藤澤政紀, 船登雅彦, 鱒見進一, 松香芳三

日歯会誌 29 62 - 66 2010

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)

Peripheral administration of botulinum toxin type A decreases exaggerated neurotransmitter release and reverses neuropathy-induced gene expression changes in trigeminal ganglia Reviewed

Ai Kumada, Yoshizo Matsuka, Igor Spigelman, Yoshihito Ishihara, Yumiko Yamamoto, Takayuki Hikasa, Wataru Sonoyama, Hiroshi kamioka, Takashi Yamashiro, Takuo Kuboki, Keiji Oguma

http://f1000.com/posters/browse/summary/87 2010

Novel Transcriptional Regulation of CCN2/CTGF by Nuclear Translocation of MMP3 Reviewed

Takanori Eguchi, Satoshi Kubota, Kazumi Kawata, Yoshiki Mukudai, Junji Uehara, Toshihiro Ohgawara, Soichiro Ibaragi, Akira Sasaki, Takuo Kuboki, Masaharu Takigawa

CCN PROTEINS IN HEALTH AND DISEASE: AN OVERVIEW OF THE FIFTH INTERNATIONAL WORKSHOP ON THE CCN FAMILY OF GENES 255 - + 2010

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

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

Surveys on splint therapy for temporomandibular disorders (TMD) -A comparison of chair time for TMD patients at university TMD clinics and private dental offices- Reviewed

Kodama N, Tsukiyama Y

J Jpn Soc TMJ 21 ( 3 ) 222 - 227 2009.12

インプラント治療における三次元石膏プリンターの有効性

吉本彰夫, 十河基文, 植村修作, 窪木拓男

日本口腔インプラント学会誌 22 ( 特別号 ) 204 - 204 2009.8

Simvastatin induces the odontogenic differentiation of human dental pulp stem cells in vitro and in vivo. Reviewed

Yosuke Okamoto, Wataru Sonoyama, Mitsuaki Ono, Kentaro Akiyama, Takuo Fujisawa, Masamitsu Oshima, Yohei Tsuchimoto, Yoshizo Matsuka, Tatsuji Yasuda, Songtao Shi, Takuo Kuboki

Journal of Endodontics Vol.35 ( No.3 ) 367 - 372 2009.3

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

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

Corrigendum to "botulinum toxin type A (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction" [Neuroscience 159 (2009) 1422-1429] (DOI:10.1016 Reviewed

Kitamura Y, Matsuka Y, Spigelman I, Ishihara Y, Yamamoto Y, Sonoyama W, Kamioka H, Yamashiro T, Kuboki T, Oguma K

Neuroscience 161 ( 3 ) 2009

Botulinum toxin blocks neurotransmitter release from somata of rat neuropathic trigeminal ganglion neurons Reviewed

Kitamura Yoichi, Matsuka Yoshizo, Ishihara Yoshihito, Spigelman Igor, Yamamoto Yumiko, Sonoyama Wataru, Kamioka Horoshi, Yamashiro Takashi, Oguma Keiji, Kuboki Takuo

TOXICON 51 6 - 6 2008.6

Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2. Reviewed International journal

Mitsuaki Ono, Satoshi Kubota, Takuo Fujisawa, Wataru Sonoyama, Harumi Kawaki, Kentaro Akiyama, Kengo Shimono, Masamitsu Oshima, Takashi Nishida, Yasuhiro Yoshida, Kazuomi Suzuki, Masaharu Takigawa, Takuo Kuboki

Cell transplantation 17 ( 1-2 ) 231 - 40 2008

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

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

粘膜圧迫により疼痛の軽減がみられた三叉神経に生じた持続性ニューロパシー性疼痛の2例 Reviewed

Yoshizo Matsuka, 熊田愛, 前川賢治, 水口一, 窪木拓男

Japanese Journal of Orofacial Pain Vol.1 ( No.1 ) 55 - 59 2008

われわれの行っているインプラント治療の臨床的検討

高木愼, 水川展吉, 福永城司, 菅原利夫, 完山学, 窪木拓男, 丸尾幸憲, 皆木省吾

岡山歯学会雑誌 26 ( 1 ) 49 - 50 2007.6

骨芽細胞様細胞(MC3T3E1)分化に対するチタンの影響

秋山謙太郎, 藤澤拓生, 明貝文夫, 大野充明, 吉田靖弘, 高柴正悟, 鈴木一臣, 窪木拓男

日本骨代謝学会学術集会プログラム抄録集 24回 229 - 229 2006.7

Effect of surface pre-treatment on durability of resin-based cements bonded to titanium. International journal

Youhei Tsuchimoto, Yasuhiro Yoshida, Maho Takeuchi, Atsushi Mine, Hirofumi Yatani, Yoh-ichi Tagawa, Bart Van Meerbeek, Kazuomi Suzuki, Takuo Kuboki

Dental materials : official publication of the Academy of Dental Materials 22 ( 6 ) 545 - 52 2006.6

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

骨芽細胞様細胞株(MC3T3E1細胞)の細胞接着,増殖,分化および遺伝子発現に対するチタンの影響

秋山謙太郎, 藤澤拓生, 明貝文夫, 完山学, 吉田靖弘, 高柴正悟, 鈴木一臣, 窪木拓男

日本口腔インプラント学会誌 19 ( 1 ) 32 - 32 2006.3

岡山大学歯学部1年次生におけるテュートリアル教育の問題点と今後の課題

完山学, 久保田聡, 市川博之, 十川紀夫, 平田あずみ, 美藤純弘, 岡本信, 福永智広, 香川智正, 中山周子, 坂本友紀, 吉田登志子, 宮脇卓也, 西村英紀, 松村誠士, 窪木拓男

岡山歯学会雑誌 24 ( 2 ) 97 - 104 2005.12

[Longitudinal follow-up of symptom severity of a patient with continuous neuropathic pain assessed by actual drug consumption record].

Chiyomi Nagamatsu, Kumiko Nawachi, Atsushi Mine, Kenji Maekawa, Takuo Kuboki

Nihon Hotetsu Shika Gakkai zasshi 49 ( 5 ) 691 - 6 2005.10

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

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.

Adsorption of polyphosphoric acid to titanium surface and its effect on hBMSC attachment Reviewed

K. Maekawa, A. Mine, T. Fujisawa, Y. Yoshida, K. Suzuki, T. Kuboki

International Congress Series 1284 332 - 333 2005.9

[Needs and current research directions of biological regenerative medicine in prosthodontic practice--to attain reliable and sophisticated dental implant therapy].

Takuo Kuboki

Nihon Hotetsu Shika Gakkai zasshi 49 ( 4 ) 576 - 86 2005.8

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.

交通事故外傷による顎顔面の変形と咬合異常を呈した症例の一治験例

藤山光治, 山城隆, 藤井昭仁, 窪木拓男, 山本照子

日本矯正歯科学会大会プログラム・抄録集 63回 301 - 301 2004.11

再生医療と歯科補綴学の接点補綴治療における再生医療のニーズと現時点での研究動向確実かつ質の高いインプラント治療をめざして

窪木拓男

日本補綴歯科学会雑誌 48 ( 112回特別 ) 41 - 41 2004.10

Regeneration of defects in articular cartilage in rat knee joints by CCN2 (connective tissue growth factor). International journal

Takashi Nishida, Satoshi Kubota, Shunji Kojima, Takuo Kuboki, Kyouji Nakao, Toshihiro Kushibiki, Yasuhiko Tabata, Masaharu Takigawa

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 19 ( 8 ) 1308 - 19 2004.8

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

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.

[Cartilage and mechanical stress from the point of the view of development, growth, pathology and therapeutic aspects].

Takuo Fujisawa, Masaharu Takigawa, Takuo Kuboki

Clinical calcium 14 ( 7 ) 29 - 35 2004.7

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

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.

掌蹠膿疱症を合併した重度歯周炎患者に対して行っている歯科的アプローチの一例

赤澤洋, 西村英紀, 前田博史, 峯篤史, 前川賢治, 窪木拓男, 高柴正悟

岡山歯学会雑誌 23 ( 1 ) 190 - 190 2004.6

Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction. International journal

Manabu Kanyama, Takuo Kuboki, Kentaro Akiyama, Kumiko Nawachi, Fabiora M Miyauchi, Hirofumi Yatani, Satoshi Kubota, Tohru Nakanishi, Masaharu Takigawa

Archives of oral biology 48 ( 10 ) 723 - 30 2003.10

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

A repetitive, steady mouth opening induced an osteoarthritis-like lesion in the rabbit temporomandibular joint

T. Fujisawa, T. Kuboki, T. Kasai, W. Sonoyama, S. Kojima, J. Uehara, C. Komori, H. Yatani, T. Hattori, M. Takigawa

Journal of Dental Research 82 ( 9 ) 731 - 735 2003

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

口腔アプライアンス療法が奏効した重度の閉塞性睡眠時無呼吸症症例 Reviewed

井上栄徳, 窪木拓男, 前川賢治, 土井郁世, 矢谷博文, 宮脇卓也, 佐藤俊樹

日本補綴歯科学会雑誌 46 ( 5 ) 649 - 654 2002.12

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

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

実際の患者の問題点に基づく少数歯欠損機能回復法に関するチュートリアル教育の試み

窪木拓男, 園山亘, 荒川光, 鈴木康司, 藤沢拓生, 小島俊司, 笠井昭夫, 上原淳二, 杉山英樹, 前川賢治, 矢谷博文

日本補綴歯科学会雑誌 46 ( 5 ) 812 - 812 2002.12

CTGF/Hcs24, a hypertrophic chondrocyte specific gene product, stimulates the proliferation and expression of the cartilage phenotype but not hypertrophy or calcification or articular cartilage in culture.

Nishida T, Kubota S, Nakanishi T, Kuboki T, Yosimichi G, Kondo S, Takigawa M

J Cell Physiol 192, 55 - 63 2002

Correlation of the near-infrared spectroscopy signals with signal intensity in T<inf>2</inf>-weighted magnetic resonance imaging of the human masseter muscle Reviewed

Takuo Kuboki, Koji Suzuki, Kenji Maekawa, Mami Inoue-Minakuchi, Claver O. Acero, Yoshinobu Yanagi, Toru Wakasa, Kanji Kishi, Hirofumi Yatani, Glenn T. Clark

Archives of Oral Biology 46 721 - 727 2001.7

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's r = 0.909, P < 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

一般歯科医院の受診患者における顎関節症の症状と徴候の変動 Reviewed

西村真紀, 景山正登, Yoshizo Matsuka, 畑中乾志, 吉田栄介, 水口一, 窪木拓男, 矢谷博文

The Journal of the Japan Association of Cranio-Mandibular Orthopedics Vol.14 ( No.1 ) 23 - 31 2001

Biomechanical calculation of human TM joint loading with jaw opening Reviewed

T Kuboki, Y Takenami, K Maekawa, M Shinoda, A Yamashita, GT Clark

JOURNAL OF ORAL REHABILITATION 27 ( 11 ) 940 - 951 2000.11

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.

超音波形成と音波形成の違いによるピンブリッジのピンホール形成精度について

吉本彰夫, 山下敦, 大西栄史, 窪木拓男, 矢谷博文

日本補綴歯科学会雑誌 44 ( 3 ) 457 - 457 2000.6

Four-Year Longitudinal Course of TMD Symptoms in an Adult Population and the Estimation of Risk Factors in Relation to Symptoms

Manabu Kamisaka, Hirofumi Yatani, Takuo Kuboki, Yoshizo Matsuka, Hajime Minakuchi

Journal of Orofacial Pain 14 ( 3 ) 224 - 232 2000

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

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.

Haemodynamic responses in chronically painful, human trapezius muscle to cold pressor stimulation

Claver O. Acero Jr, Takuo Kuboki, Kenji Maekawa, Atsushi Yamashita, Glenn T. Clark

Archives of Oral Biology 44 ( 10 ) 805 - 812 1999.10

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

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

Direct adenovirus-mediated gene delivery to the temporomandibular joint in guinea-pigs

Takuo Kuboki, Tohru Nakanishi, Manabu Kanyama, Wataru Sonoyama, Takuo Fujisawa, Kappei Kobayashi, Takumi Ikeda, Toshikazu Kubo, Atsushi Yamashita, Masaharu Takigawa

Archives of Oral Biology 44 ( 9 ) 701 - 709 1999.9

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

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

Effect of intravenous infusion of a β-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold-pressor stimulation

Kenji Maekawa, Takuo Kuboki, Takuya Miyawaki, Masahiko Shimada, Atsushi Yamashita, Glenn T. Clark

Archives of Oral Biology 44 ( 6 ) 475 - 483 1999.6

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

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

ピンブリッジ法の予後調査と新しい超音波形成器によるピンホール形成の試み

吉本彰夫, 山下敦, 窪木拓男, 白井知恵子, 今井誠

日本補綴歯科学会雑誌 43 ( 101回特別 ) 193 - 193 1999.5

周期的な機械的ストレスを培養軟骨細胞に加え続けると,MMP及びIL-1の発現が誘導され,細胞外マトリックスの分解が引き起こされる

Fujisawa Takuo, Hattori Takako, Takahashi Kojiro, Kuboki Takuo, Yamashita Atsushi, Takigawa Masaharu

The Journal of Biochemistry 125 ( 5 ) 966 - 975 1999.5

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

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

Specific antibodies against human cultured chondrosarcoma (HCS-2/8)and osteosarcoma(Saos-2)cells detected in the serum of the TMJ osteoarthritis patients.(共著)

Takuo Kuboki, Takako Hattori, Tsunehisa Mizushima, Manabu Kanyama, Takuo Fujisawa, Atsushi Yamashita, Masaharu Takigawa

Archs Oral Biol 44 ( 5 ) 403 - 414 1999.5

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

Effect of intravenous infusion of an α-adrenergic blocking agent on the haemodynamic changes in human masseter muscle induced by cold pressor stimulation

Kenji Maekawa, Takuo Kuboki, Takuya Miyawaki, Masahiko Shimada, Atsushi Yamashita, Glenn T. Clark

Archives of Oral Biology 44 ( 4 ) 319 - 327 1999.4

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

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

Haemodynamic response to cold pressor stimulation on chronically painful trapezius muscle Reviewed

C.O.Acero, Jr, T.Kuboki, K.Maekawa, A.Yamashita, G.T.Clark

Arch Oral Biol 1999

Connective tissue growth factor induces the proliferation, migration, and tube formation of vascular endothelial cells in vitro, and angiogenesis in vivo

Tsuyoshi Shimo, Tohru Nakanishi, Takashi Nishida, Masahiro Asano, Manabu Kanyama, Takuo Kuboki, Takuya Tamatani, Katsunari Tezuka, Motohide Takemura, Tomohiro Matsumura, Masaharu Takigawa

Journal of Biochemistry 126 ( 1 ) 137 - 145 1999

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

Cyclic mechanical stress induces extracellular matrix degradation in cultured chondrocytes via gene expression of matrix metalloproteinases and interleukin-1

Takuo Fujisawa, Takako Hattori, Kojiro Takahashi, Takuo Kuboki, Atsushi Yamashita, Masaharu Takigawa

Journal of Biochemistry 125 ( 5 ) 966 - 975 1999

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

The effects of sustained incisal clenching on the temporomandibular joint space

Y. Takenami, T. Kuboki, C. O. Acero Jr., K. Maekawa, A. Yamashita, Y. Azuma

Dentomaxillofacial Radiology 28 ( 4 ) 214 - 218 1999

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

Effect of Occlusal Appliances and Clenching on the Internally Deranged TMJ Space

Takuo Kuboki, Yasushi Takenami, Maria G. Orsini, Kenji Maekawa, Atsushi Yamashita, Yoshiharu Azuma, Glenn T. Clark

Journal of Orofacial Pain 13 ( 1 ) 38 - 48 1999

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.

Clinical Predictability of Temporomandibular Joint Disc Displacement

M. G. Orsini, T. Kuboki, S. Terada, Y. Matsuka, H. Yatani, A. Yamashita

Journal of Dental Research 78 ( 2 ) 650 - 660 1999

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

A asessment of the relationship between trapezius muscle pain and skin surface temperature using infrared thermography.

川端秀治, 前川賢治, 窪木拓男, 山下敦, 若狭亨, 岸幹二

岡山歯学会雑誌 18 ( 1 ) 251 - 258 1999

Cold pressor stimulus temperature and resting masseter muscle haemodynamics in normal humans

Kenji Maekawa, Takuo Kuboki, G. T. Clark, Motoki Shinoda, Atsushi Yamashita

Archives of Oral Biology 43 ( 11 ) 849 - 859 1998.11

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

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

Macroscopic osseous changes in the temporomandibular joint related to dental attrition in Japanese macaque skull. Reviewed

Yoshizo Matsuka, T Iijima, K Suzuki, T Kuboki, A Yamashita

Journal of Oral Rehabilitation Vol.25 ( No.9 ) 687 - 693 1998.9

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

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 < 0.001). A strong relation was observed between age and dental attrition (P < 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.

The relationship between signs and symptoms of temporomandibular disorders and bilateral occlusal contact patterns during lateral excursions

E. K. Watanabe, H. Yatani, T. Kuboki, Y. Matsuka, S. Terada, M. G. Orsini, A. Yamashita

Journal of Oral Rehabilitation 25 ( 6 ) 409 - 415 1998

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

Diagnostic value of 4 criteria to interpret temporomandibular joint normal disk position on magnetic resonance images

M. Gabriela Orsini, Takuo Kuboki, Shohei Terada, Yoshizo Matsuka, Atsushi Yamashita, Glenn T. Clark

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 86 ( 4 ) 489 - 497 1998

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

The Validity of clinical examination for diagnosing anterior disk displacement without reduction. (共著)

YATANI H

Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 85 654 - 660 1998

Viscoelastic properties of the pig temporomandibular joint articular soft tissues of the condyle and disc Reviewed

T Kuboki, M Shinoda, MG Orsini, A Yamashita

JOURNAL OF DENTAL RESEARCH 76 ( 11 ) 1760 - 1769 1997.11

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.

ニホンザル顎関節の形態計測学的研究 Reviewed

Yoshizo Matsuka, 飯島輝明, 鈴木康司, 窪木拓男, 矢谷博文, 山下敦, 上月生也, 鈴木秀典

京都大学霊長類研究所年報 Vol.26 81 - 81 1997

Long-term follow-up study on drop-out TMD patients with self-administered questionnaires

Hirofumi Yatani, Takushi Kaneshima, Takuo Kuboki, Akio Yoshimoto, Yoshizo Matsuka, Atsushi Yamashita

Journal of Orofacial Pain 11 ( 3 ) 258 - 269 1997

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

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.

The influence of observer calibration in temporomandibular joint magnetic resonance imaging diagnosis

M. Gabriela Orsini, Shohei Terada, Takuo Kuboki, Yoshizo Matsuka, Atsushi Yamashita

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 84 ( 1 ) 82 - 87 1997

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

The effect of occlusal appliances and clenching on the temporomandibular joint space

Takuo Kuboki, Yoshiharu Azuma, Maria G. Orsini, Tetsuhiko Hirooka, Hirofumi Yatani, Atsushi Yamashita

Journal of Orofacial Pain 11 ( 1 ) 67 - 77 1997

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.

The effect of occlusal appliances and clenching on the temporomandibular joint space

Takuo Kuboki, Yoshiharu Azuma, Maria G. Orsini, Tetsuhiko Hirooka, Hirofumi Yatani, Atsushi Yamashita

Journal of Orofacial Pain 11 ( 1 ) 67 - 77 1997

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.

Temporomandibular disorders in the adult population of Okayama city, Japan

Yoshizo Matsuka, Hirofumi Yatani, Takuo Kuboki, Atsushi Yamashita

Cranio 14 ( 2 ) 158 - 162 1996

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

Effects of sustained unilateral molar clenching on the temporomandibular joint space

Takuo Kuboki, Yoshiharu Azuma, Maria G. Orsini, Yasushi Takenami, Atsushi Yamashita

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 82 ( 6 ) 616 - 624 1996

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

Effects of sustained unilateral molar clenching on the temporomandibular joint space

Takuo Kuboki, Yoshiharu Azuma, Maria G. Orsini, Yasushi Takenami, Atsushi Yamashita

Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics 82 ( 6 ) 616 - 624 1996

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

Changes of Joint Space Distribution during Jaw Opening on Sagittal Helical Blurring Motion Tomograms of the TMJ

武並康史, 窪木拓男, 東義晴, 矢谷博文, 山下敦

J. Jpn. Prosthodont. Soc. 40 ( 4 ) 702 - 709 1996

Clinical Procedures and Evaluation of a Pin Bridge Technique Supported by Titanium-Nickel Shape Memory Alloy Pins

山下敦, 今井誠, 窪木拓男, 白井知恵子, 岡本壮一郎

J. Jpn. Prosthodont. Soc. 40 ( 96回特別 ) 77 1996

Reliability of the assisted Maximum Opening Measurement Patr 1. Development of a Measuring Device with a Computer-aided Passive Steretch Mechanism

篠田一樹, 山下敦, 水口一, 前川賢治, 寺田昌平, 窪木拓男

J. Jpn. Prosthodont. Soc. 40 ( 96回特別 ) 98 1996

Subcategorization of the TMD Patients with their Initial Chief Complaints obtained by a Self-administered Questionnair

鈴木康司, 山下敦, 園山亘, 寺田昌平, 窪木拓男

J. Jpn. Prosthodont. Soc. 40 ( 96回特別 ) 149 1996

Clinical Evaluation of New Light-Curing Composite Resin using for Appliarce Therapy of Patients with Temporomaudibular Disorders

矢谷博文, 窪木拓男, 神桂二, 山下敦

J. Okayama Dent. Soc. 13 ( 1 ) 127 - 134 1994

Stress-Transfer Characteristics of Stress-Absorbing Elements in the IMZ Implant System Part(]G0002[), Stress around a Freestanding Single Implant under Dynamic Loading Conditions

Sato Masaki, Kuboki Takuo, Yamashita Atsushi

J. Jpn. Prosthodont. Soc. 37 ( 4 ) 744 - 753 1993.8

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

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

A case report of two patients with closed lock whose condition of disk displacement without reduction improved to disk displacement with reduction after occlusal reconstruction.

矢谷博文, 窪木拓男, 山下敦

日本口腔科学会雑誌 42 ( 1 ) 159 - 166 1993

A newly-developed eualuation method for the occlusal force of fixed-bridge restoration supported by the combination of tooth and osseointegrated Titanium implants

板阪宗生, 窪木拓男, 佐藤正喜, 山下敦, 松村智弘

J. Okayama Dent. Soc. 12 ( 1 ) 123 - 130 1993

Clinical Application of the Functional Analysis of the Stomatognathic System for Implant Prosthesis before Treatment

佐藤正喜, 窪木拓男, 板阪宗生, 近藤康弘, 山下敦, 高木慎, 西嶋克巳, 上山吉哉, 松村智弘

J. Okayama Dent. Soc. 12 ( 1 ) 131 - 143 1993

Stress-Transfer Characteristics of Stress-Absorbing Elements in the IMZ Implant, Part1, Stress around a Freestanding Single Implant under Static Loading Conditions

Sato Masaki, Kuboki Takuo, Itasaka Muneo, Kondo Yasuhiro, Yamashita Atsushi

J. Jpn. Prosthodont. Soc. 36 ( 5 ) 1102 - 1110 1992.10

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

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

Biomechanical Analysis of Stomatognathic System during Power Stroke of Unilateral Chewing

KUBOKI T.

J. Jpn. Soc. TMJ 3 ( 2 ) 66 - 78 1991

顎関節部負荷ならびに顎関節構造の対負荷特性に関する生物力学的研究(第1編) 近似的顎関節負荷モデルの構築

窪木拓男

岡山歯学会雑誌 9 ( 1 ) 179 - 195 1990.6

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

A CASE-REPORT OF A PATIENT WITH UNILATERAL ANTERIOR DISK DISPLACEMENT (RECIPROCAL CLICKING) FINALIZED BY OCCLUSAL PORCELAIN BONDING

H YATANI, T KUBOKI, Y AMANO, A YAMASHITA

PATHOPHYSIOLOGY OF HEAD AND NECK MUSCULOSKELETAL DISORDERS 7 27 - 33 1990

Biomechanical studies on temporomandibular joint loadings and indentative effects of the loads on the joint structures

KUBOKI T.

The Journal of Okayama Dental Society 9 ( 1 ) 179 - 227 1990

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