Do carbon nanotubes control bone remodeling?

2013 Fiscal Year Final Research Report

• 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
• Keywords: 破骨細胞 / 骨芽細胞 / カーボンナノチューブ / 石灰化

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 osteoporotic bone mass via Cnot3. Stability of mRNA influences osteoporotic bone mass via CNOT3 (2014)
  • Author(s): Watanabe C, Morita M, Hayata T, Nakamoto T, Kikuguchi C, Li X, Kobayashi Y, Takahashi N, Notomi T, Moriyama K, Yamamoto T, Ezura Y, Noda M
  • Journal Title: Proc Natl Acad Sci USA Volume: 111 Pages: 2692-2697
  • DOI: 10.1073/pnas.1316932111
• [Journal Article] Noncanonical Wnt5a enhances Wnt/β-catenin signaling during osteoblastogenesis (2014)
  • Author(s): Okamoto M, Udagawa N, Uehara S, Maeda K, Yamashita T, Nakamichi Y, Kato H, Saito N, Minami Y, Takahashi N, Kobayashi Y
  • Journal Title: Sci Rep Volume: 4 Pages: 4493
  • DOI: 10.1038/srep04493
• [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 Pages: 85878
  • DOI: 10.1371/journal.pone.0085878
• [Journal Article] Roles of Wnt signals in bone resorption during physiological and pathological states (2013)
  • Author(s): Maeda K, Takahashi N, Kobayashi Y
  • Journal Title: J Mol Med Volume: 91 Pages: 15-23
  • DOI: 10.1007/s00109-012-0974-0
• [Journal Article] Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis (2013)
  • Author(s): Horibe K; Nakamichi Y; Uehara S; Nakamura M; Koide M; Kobayashi Y, Takahashi N, Udagawa N
  • Journal Title: Immunology Volume: 140 Pages: 344-351
  • DOI: 10.1111/imm.12146
• [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 Pages: 486-495
  • DOI: 10.1007/s00774-013-0476-3
• [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, Kobayashi Y, Ninomiya T, Nakamura M, Yasuda H, Arai Y, Okahashi N, Yoshinari N, Takahashi N, Udagawa N
  • Journal Title: Endocrinology Volume: 154 Pages: 773-782
  • DOI: 10.1210/en.2012-1928
• [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: Adv Mater Volume: 24(16) Pages: 2176-2185
  • DOI: 10.1002/adma.201103832
• [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 Pages: 175-181
  • DOI: 10.5312/wjo.v3.i11.175
• [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 Pages: 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 CSF-1^<op/op>mice (2012)
  • Author(s): Nakamichi Y, Mizoguchi T, Arai A, Kobayashi Y, Sato M, Penninger JM, Yasuda H, Kato S, DeLuca HF, Suda T, Udagawa N, Takahashi N
  • Journal Title: Proc Natl Acad Sci UAS Volume: 109 Pages: 10006-10011
  • DOI: 10.1073/pnas.1207361109
• [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, Mizoguchi T, Harada S, Kobayashi Y, Nakamichi Y, Yasuda H, Penninger JM, Yamada K, Udagawa N, Takahashi N
  • Journal Title: J Cell Science Volume: 125 Pages: 2910-2917
  • DOI: 10.1242/jcs.099986
• [Journal Article] Wnt5a-Ror2 signaling between osteoblast-lineage cells 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 TJ, Minami Y, Takahashi N
  • Journal Title: Nature Med Volume: 18 Pages: 405-412
  • DOI: 10.1038/nm.2653
• [Journal Article] Bone Effects of vitamin D -Discrepancies between in vivo and in vitro studies - (2012)
  • Author(s): Suda T, Takahashi F, Takahashi N
  • Journal Title: Arch Biochem Biophys Volume: 523 Pages: 22-29
  • DOI: 10.1016/j.abb.2011.11.011
• [Journal Article] Regulation of Osteoclast Function (2012)
  • Author(s): Nakamura I, Takahashi N, Jimi E, Udagawa N, Suda T
  • Journal Title: Mod Rheumatol Volume: 22 Pages: 167-177
  • DOI: 10.1007/s10165-011-0530-8
• [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
• [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)
  • Total Pages: 57-63
  • 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)
  • Total Pages: 16-7
  • 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)
  • Total Pages: 30-38
  • 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)
  • Total Pages: 40-46
  • Publisher: メディカルレビュー社
• [Remarks]
  • URL: http://www.mdu.ac.jp/graduate/index.html