研究者詳細 - 窪木　拓男

論文 - 窪木　拓男

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

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年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

DOI： 10.1016/j.joen.2008.11.024

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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 査読

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

Neuroscience 161 ( 3 ) 2009年

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

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年6月

Promotion of hydroxyapatite-associated, stem cell-based bone regeneration by CCN2. 査読国際誌

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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：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

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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例査読

松香芳三, 熊田愛, 前川賢治, 水口一, 窪木拓男

日本口腔顔面痛学会雑誌 Vol.1 ( No.1 ) 55 - 59 2008年

記述言語：日本語出版者・発行元：(一社)日本口腔顔面痛学会

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例を経験した。症例1は62歳女で、上顎左側第二小臼歯、第一大臼歯に無麻酔下で歯根面のキュレッテージを受けた後、疼痛を自覚するようになった。根管治療を受け、一時的な症状軽減を認めたが、疼痛が再発した。抜歯後も疼痛が持続し、三叉神経痛の診断で薬物療法を受けたが無効であった。シーネによる疼痛部位の粘膜圧迫、カプサイシン+ベンゾカインの併用、塩酸アミトリプチンリン、アルプラゾラム、エトドラクなどの内服が効果を示した。症例2は47歳女で、腰痛の治療中に上顎左側臼歯部の違和感で、上顎左側第二大臼歯の根管治療を行うが症状の変化は見られなかった。シーネによる圧迫とベンゾカインの併用は効果があった。

DOI： 10.11264/jjop.1.55

J-GLOBAL

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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年6月

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年7月

Effect of surface pre-treatment on durability of resin-based cements bonded to titanium. 国際誌

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年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：ELSEVIER SCI LTD

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

DOI： 10.1016/j.dental.2005.08.002

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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年3月

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年12月

服薬状況を用いて評価した持続性神経障害性とう痛患者の長期治療経過

永松千代美, 永松千代美, 縄稚久美子, 縄稚久美子, 峯篤史, 峯篤史, 前川賢治, 前川賢治, 窪木拓男, 窪木拓男

日本補綴歯科学会雑誌 49 ( 5 ) 691 - 6 2005年10月

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

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

International Congress Series 1284 332 - 333 2005年9月

《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 49 ( 4 ) 576 - 86 2005年8月

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年11月

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年10月

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

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年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

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

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[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年7月

記述言語：日本語掲載種別：研究論文（学術雑誌）

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

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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年6月

Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction. 国際誌

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年10月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD

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

DOI： 10.1016/S0003-9969(03)00153-5

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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年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Intern. and American Associations for Dental Research

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

DOI： 10.1177/154405910308200914

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論文 - 窪木 拓男

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論文 - 窪木　拓男