Do carbon nanotubes control bone remodeling?

• Project/Area Number: 24659833
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Functional basic dentistry
• Research Institution: Matsumoto Dental University
• Principal Investigator: TAKAHASHI Naoyuki 松本歯科大学, 総合歯科医学研究所, 教授 (90119222)
• Co-Investigator(Kenkyū-buntansha): KAWAHARA Ichiro 松本歯科大学, 歯学部, 准教授 (20319114) ; NAKAMICHI Yuko 松本歯科大学, 総合歯科医学研究所, 講師 (20350829) ; UEHARA Shunsuke 松本歯科大学, 歯学部, 講師 (90434480)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 破骨細胞 / 骨芽細胞 / カーボンナノチューブ / 石灰化 / チタン / エピタキシー因子

Research Abstract

Much attention has been focused in recent years on the applications of carbon nanotubes (CNTs) as biomaterials. Application of CNTs to the regenerative medicine including bone regeneration is studied in particular as CNTs have been reported to be useful scaffold materials. In the process in which the skeletal metabolism action of CNT is analyzed, we found two new functions. (1) CNT taken in osteoclast precursors inhibited nuclear translocation of NFATc1, an indispensable transcription factor for osteoclastogenesis, to suppress osteoclastic differentiation. (2) CNTs promote osteoblast differentiation by causing local accumulation of Ca. CNTs served as nuclei of hydroxyapatite crystallization and induced calcification with the help of alkaline phosphatase released by osteoblasts. This synergistic effect promotes bone formation. We have established a new concept that the CNT act as a regulator of bone remodelling.

Research Products

• [Journal Article] Osteoclast Cell Lineage (2014)
  • Author(s): Takahashi N, Mizoguchi T, Nakamichi Y, Kobayashi Y, Nakamura M, Willy Hofstetter W, Udagawa N
  • Journal Title: Characteristics and behavior of osteoclast precursors in vivo Encyclopedia of Human Body 3^<rd> Edition Volume: (in press)
• [Journal Article] Osteoclasts polarize on dental implant materials as if they were on bone (2014)
  • Author(s): Nakayama T, Thirukond GJ, Nagasaw S, Kawahara I, Udagawa N, Yagami K, Kawatani M, Osada H, Doi Y, Yoshinaria N, Takahashi N
  • Journal Title: J Oral Biosci Volume: (in press)
• [Journal Article] Stability of mRNA influences steoporotic bone mass via CNOT3 (2014)
  • Author(s): Watanabe, C. Morita, M. Yamamoto T. (13名)
  • Journal Title: Natl Acad Sci U S A Volume: Vol.111 Issue: 7 Pages: 2692-2697
  • DOI: 10.1073/pnas.1316932111
  • Peer Reviewed / Open Access
• [Journal Article] Noncanonical Wnt5a enhances Wnt/&#61538;-catenin signaling during osteogenesis. (2014)
  • Author(s): Okamoto, M., Udagawa, N., Yamashita, T., Nakamichi, Y., Uehara, S., Kato, H., Saito, N., Minami, Y., Takahashi, N., Kobayashi, Y.
  • Journal Title: Sci. report Volume: 4 Issue: 1 Pages: 4493-4493
  • DOI: 10.1038/srep04493
  • Peer Reviewed / Open Access
• [Journal Article] Arctigenin inhibits osteoclast differentiation and function by suppressing both calcineurin-dependent and osteoblastic cell-dependent NFATc1 pathways. (2014)
  • Author(s): Yamashita T, Uehara S, Udagawa N, Li F, Kadota S, Esumi H, Kobayashi Y, Takahashi N
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: 85878-85878
  • DOI: 10.1371/journal.pone.0085878
  • Peer Reviewed / Open Access
• [Journal Article] Roles of Wnt signals in bone resorption during physiological and pathological states. (2013)
  • Author(s): Maeda K et al.
  • Journal Title: J Mol Med (Berl) Volume: 91 Issue: 1 Pages: 15-23
  • DOI: 10.1007/s00109-012-0974-0
  • Peer Reviewed / Open Access
• [Journal Article] Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis (2013)
  • Author(s): Horibe K, Kobayashi Y, Takahashi N, Udagawa N(他4名)
  • Journal Title: Immunology Volume: 140 Issue: 3 Pages: 344-351
  • DOI: 10.1111/imm.12146
  • Peer Reviewed / Open Access
• [Journal Article] IL-34 and CSF-1 similarities and differences (2013)
  • Author(s): Nakamichi Y, Udagawa N, Takahashi N
  • Journal Title: J Bone Miner Metab Volume: 31 Issue: 5 Pages: 486-495
  • DOI: 10.1007/s00774-013-0476-3
  • NAID: 10031201682
  • Peer Reviewed / Open Access
• [Journal Article] Osteoprotegerin-deficient male mice as a model for severe alveolar bone loss: Comparison with RANKL-overexpressing transgenic male mice. (2013)
  • Author(s): Koide M et al.
  • Journal Title: Endocrinology Volume: 190 Issue: 2 Pages: 773-782
  • DOI: 10.1210/en.2012-1928
  • Peer Reviewed / Open Access
• [Journal Article] Mechanism of inhibitory action of Eldecalcitol, an active vitamin D analog, on bone resorption in vivo (2013)
  • Author(s): Takahashi N
  • Journal Title: J Steroid Biochem Mol Biol Volume: 136(pii : S0960-0760(12)00243-9) Pages: 171-174
• [Journal Article] Carbon nanotubes induce bone calcification by bidirectional interaction with osteoblasts (2012)
  • Author(s): Shimizu M, Kobayashi Y, Mizoguchi T, Nakamura H, Kawahara I, Narita N, Usui Y, Aoki K, Hara K, Haniu H, Ogihara N, Ishigaki N, Nakamura K, Kato H, Kawakubo M, Dohi Y, Taruta S, Kim YA, Endo M, Ozawa H, Udagawa N, Takahashi N, Saito N
  • Journal Title: Advanced Materials Volume: 24 Issue: 16 Pages: 2176-2185
  • DOI: 10.1002/adma.201103832
  • Peer Reviewed
• [Journal Article] New roles of osteoblasts involved in osteoclast differentiation. (2012)
  • Author(s): Yamashita T, Takahashi N, Udagawa N
  • Journal Title: World J Osteoarthritis Volume: 3 Issue: 11 Pages: 175-181
  • DOI: 10.5312/wjo.v3.i11.175
  • Peer Reviewed
• [Journal Article] c-Fms signaling mediates neurofibromatosis type-1 osteoclast gain-in-functions (2012)
  • Author(s): He Y, Rhodes SD, Chen S, Wu X, Yuan J, Yang X, Jiang L, Li X, Takahashi N, Xu M, Mohammad KS, Guise TA, Yang FC
  • Journal Title: PLOS ONE Volume: 7 Issue: 11 Pages: 46900-46900
  • DOI: 10.1371/journal.pone.0046900
• [Journal Article] Spleen serves as a reservoir of osteoclast precursors through vitamin D-induced IL-34 expression in osteopetrotic op/op mice. (2012)
  • Author(s): Nakamichi Y et al.
  • Journal Title: Proc Natl Acad Sci USA Volume: 109 Issue: 25 Pages: 10006-10011
  • DOI: 10.1073/pnas.1207361109
  • Peer Reviewed
• [Journal Article] c-Fos plays an essential role in the up-regulation of RANK expression in osteoclast precursors within the bone microenvironment (2012)
  • Author(s): Arai A, et al
  • Journal Title: J Cell Sci Volume: (印刷中) Pages: 2910-2917
  • DOI: 10.1242/jcs.099986
  • Peer Reviewed
• [Journal Article] Wnt5a-Ror2 signaling between osteoblasts and osteoclast precursors enhances osteoclastogenesis (2012)
  • Author(s): Maeda, K., Kobayashi, Y., Udagawa, N., Uehara, S., Ishihara, A., Mizoguchi, T., Kikuchi, Y., Takada, I., Kato, S., Kani, S., Nishita, M., Marumo, K., Martin, T.J., Minami, Y., Takahashi, N.
  • Journal Title: Nat.Med. Volume: (印刷中) Issue: 3 Pages: 405-12
  • DOI: 10.1038/nm.2653
  • Peer Reviewed
• [Journal Article] Bone Effects of vitamin D -Discrepancies between in vivo and in vitro studies -. (2012)
  • Author(s): Suda T
  • Journal Title: Arch Biochem Biophys Volume: 523 Issue: 1 Pages: 22-29
  • DOI: 10.1016/j.abb.2011.11.011
  • Peer Reviewed
• [Journal Article] Regulation of Osteoclast Function. Mod Rheumatol, 22:167-177, 2012.Suda T, Takahashi F, Takahashi N Bone Effects of vitamin D-Discrepancies between in vivo and in vitro studies - (2012)
  • Author(s): Nakamura I, Takahashi N, Jimi E, Udagawa N, Suda T
  • Journal Title: Arch Biochem Biophys Volume: 523 Issue: 2 Pages: 22-29
  • DOI: 10.1007/s10165-011-0530-8
  • Peer Reviewed
• [Presentation] 歯周病において破骨細胞はどのように誘導されるか (2014)
  • Author(s): 高橋直之
  • Organizer: 第57回春季日本歯周病学会
  • Place of Presentation: 岐阜
  • Year and Date: 2014-05-23
• [Presentation] チタンインプラント埋入における生体側のイベントII (2013)
  • Author(s): 高橋直之
  • Organizer: Dentistry Quo Vadis?
  • Place of Presentation: 東京
  • Year and Date: 2013-12-08
• [Presentation] 骨芽細胞と破骨細胞、そして力の関係 (2013)
  • Author(s): 高橋直之
  • Organizer: Dentistry、Quo Vadis?
  • Place of Presentation: 東京
  • Year and Date: 2013-12-07
• [Presentation] 破骨細胞の分化と機能を調節するRANKL-RANKシグナル (2013)
  • Author(s): 高橋直之
  • Organizer: 城北骨代謝フォーラム東京
  • Place of Presentation: 東京
  • Year and Date: 2013-10-29
• [Presentation] インプラントはOsseointegrationをどのように獲得するか (2013)
  • Author(s): 高橋直之
  • Organizer: 松本歯科大学インプラントカンファレンス
  • Place of Presentation: 塩尻
  • Year and Date: 2013-06-10
• [Presentation] Mechanism of anti-bone resorptive action of eldecalcitol (2013)
  • Author(s): Naoyuki Takahashi
  • Organizer: Advisory meeting of active vitamin D
  • Place of Presentation: Kobe
  • Year and Date: 2013-05-28
• [Presentation] TRAP marks as vestiges of polarized osteoclasts (2013)
  • Author(s): Naoyuki Takahashi
  • Organizer: 6^<th> International symposium on the biology of tartrate resistant acid phosphatase
  • Place of Presentation: Kobe
  • Year and Date: 2013-05-27
• [Presentation] 破骨細胞の分化と機能の調節機構 (2013)
  • Author(s): 高橋直之
  • Organizer: 第86回日本整形外科学会学術総会
  • Place of Presentation: 広島
  • Year and Date: 2013-05-23
• [Presentation] 骨吸収を調節するWntシグナル (2013)
  • Author(s): 高橋直之
  • Organizer: 第4回彩の国骨フォーラム
  • Place of Presentation: 埼玉
  • Year and Date: 2013-02-08
• [Presentation] 破骨細胞前駆細胞を制御する骨芽細胞の新しい役割 (2013)
  • Author(s): 高橋直之
  • Organizer: 第15回骨とリウマチ研究会
  • Place of Presentation: 東京
  • Year and Date: 2013-01-31
• [Presentation] 破骨細胞の分化を調節する骨芽細胞の新しい役割 (2012)
  • Author(s): 高橋直之
  • Organizer: 創価大学セミナー
  • Place of Presentation: 東京
  • Year and Date: 2012-11-16
• [Presentation] 破骨細胞はどのように骨を認識し極性化するか (2012)
  • Author(s): 高橋直之
  • Organizer: 日本歯科理工学会・中部支部夏季セミナー
  • Place of Presentation: 妙高高原
  • Year and Date: 2012-08-23
• [Presentation] Mechanism of inhibitory action of eldecalcitol, an active vitamin D analog, on bone resorption in vivo (2012)
  • Author(s): Naoyuki Takahashi
  • Organizer: 5^<th> Workshop on Vitamin D
  • Place of Presentation: Huston
  • Year and Date: 2012-06-22
• [Presentation] TRAP marks as vestiges of polarized osteoclasts. 6th International symposium on the biology of tartrate resistant acid phosphatase.
  • Author(s): Naoyuki Takahashi
  • Organizer: 6th International symposium on the biology of tartrate resistant acid phosphatase.
  • Place of Presentation: 神戸ポートピアホテル（兵庫県、神戸市）
  • Invited
• [Presentation] Mechanism of anti-bone resorptive action of eldecalcitol.
  • Author(s): Naoyuki Takahashi
  • Organizer: Advisory meeting of active vitamin D
  • Place of Presentation: 神戸ポートピアホテル（兵庫県、神戸市）
  • Invited
• [Presentation] 破骨細胞の分化と機能の調節機構
  • Author(s): 高橋直之
  • Organizer: 第86回日本整形外科学会学術総会
  • Place of Presentation: 広島グリーンアリーナ[広島県、広島市）
  • Invited
• [Presentation] 骨芽細胞と破骨細胞、そして力の関係
  • Author(s): 高橋直之
  • Organizer: Dentistry、Quo Vadis?
  • Place of Presentation: 星陵会館（東京都、千代田区）
  • Invited
• [Presentation] チタンインプラント埋入における生体側のイベント
  • Author(s): 高橋直之
  • Organizer: Dentistry Quo Vadis?
  • Place of Presentation: 星陵会館 (東京）
  • Invited
• [Presentation] 破骨細胞はどのように骨を認識し極性化するか
  • Author(s): 高橋直之
  • Organizer: 日本歯科理工学会・中部支部夏季セミナー
  • Place of Presentation: 赤倉ホテル（新潟県妙高市）
  • Invited
• [Book] "破骨細胞はどのようにして骨組織にのみ形成されるのか"骨代謝実験医学臨時増刊号(田中栄編) (2014)
  • Author(s): 高橋直之(分担執筆)
  • Publisher: 羊土社
• [Book] "カルシトニンと骨・ミネラル代謝"副甲状腺・骨代謝疾患診療マニュアル(竹内靖博編) (2013)
  • Author(s): 小出雅則,高橋直之(分担執筆)
  • Publisher: 診断と治療社
• [Book] "ビスホスホネートの作用機構"ファーマナビゲータービスホスホネート編2(松本俊夫、萩野浩編) (2013)
  • Author(s): 小出雅則,高橋直之(分担執筆)
  • Publisher: メディカルレビュー社
• [Book] "ビタミンDのカルシウム代謝調節機構"ファーマナビゲーター活性型ビタミンD_3製剤編(太田博明、松本俊夫編) (2012)
  • Author(s): 高橋直之(分担執筆)
  • Publisher: メディカルレビュー社
• [Remarks]
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• [Remarks] 松本歯科大学大学院ホームページ
  • URL: http://www.mdu.ac.jp/graduate/index.html
• [Remarks] 松本歯科大学大学院ホームページ
  • URL: http://www.mdu.ac.jp/graduate/index.html