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Elucidation of Wnt signaling network controlling bone metabolism

Research Project

Project/Area Number 25221310
Research Category

Grant-in-Aid for Scientific Research (S)

Allocation TypeSingle-year Grants
Research Field Functional basic dentistry
Research InstitutionMatsumoto 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) Udagawa Nobuyuki  松本歯科大学, 歯学部, 教授 (70245801)
Kobayashi Yasuhiro  松本歯科大学, 総合歯科医学研究所, 教授 (20264252)
Nakamura Hiroaki  松本歯科大学, 歯学部, 教授 (50227930)
Taguchi Akira  松本歯科大学, 歯学部, 教授 (70243582)
Project Period (FY) 2013-05-31 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥131,820,000 (Direct Cost: ¥101,400,000、Indirect Cost: ¥30,420,000)
Fiscal Year 2015: ¥37,310,000 (Direct Cost: ¥28,700,000、Indirect Cost: ¥8,610,000)
Fiscal Year 2014: ¥36,010,000 (Direct Cost: ¥27,700,000、Indirect Cost: ¥8,310,000)
Fiscal Year 2013: ¥58,500,000 (Direct Cost: ¥45,000,000、Indirect Cost: ¥13,500,000)
Keywords破骨細胞 / 骨芽細胞 / Wnt / RANKL / OPG / 骨代謝共役 / Wnt / OPG / RANKL
Outline of Final Research Achievements

Osteoclasts resorb old bone, and osteoblasts make new bone at the resorption site. Therefore, bone tissue is re-formed throughout the life. Although bone formation by osteoblasts is tightly coupled with bone resorption by osteoclasts, the molecular mechanism of the coupling phenomena is unknown. Wnt signaling is an important signal that regulates bone metabolism. In the present study, we showed that (1) Wnt molecules, which osteoclasts and osteoblasts secrete, strictly regulate bone metabolism, (2) osteoclasts regulates osteoblast function through the control of the Wnt signaling, and (3) Wnt signal regulatory agents will become good drugs for osteoporosis treatment.

Assessment Rating
Verification Result (Rating)

B

Assessment Rating
Result (Rating)

A-: Progress in the research is steadily towards the initial goal. However, further efforts are necessary as a part of the research progress is delayed.

Report

(8 results)
  • 2016 Research Progress Assessment (Verification Result) ( PDF )
  • 2015 Annual Research Report   Abstract(Research Progress Assessment) ( PDF )   Research Progress Assessment (Result) ( PDF )   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Abstract ( PDF )   Annual Research Report
  • Research Products

    (22 results)

All 2016 2015 2014 2013

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 14 results,  Acknowledgement Compliant: 2 results) Presentation (8 results) (of which Invited: 8 results)

  • [Journal Article] The dynamin inhibitor dynasore inhibits bone resorption by rapidly disrupting actin rings of osteoclasts.2016

    • Author(s)
      Thirukonda GJ, Uehara S, Nakayama T, Yamashita T, Nakamura Y, Mizoguchi T, Takahashi N, Yagami K, Udagawa N, Kobayashi Y
    • Journal Title

      J Bone Miner Metab

      Volume: 34

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Wnt16 regulates osteoclast differentiation in conjunction with Wnt5a.2015

    • Author(s)
      Kobayashi Y, Thirukonda GJ, Nakamura Y, Koide M, Yamashita T, Uehara S, Kato H, Udagawa N, Takahashi N
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 463 Issue: 4 Pages: 1278-1283

    • DOI

      10.1016/j.bbrc.2015.06.102

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The regulation of osteoclast differentiation by Wnt signals.2015

    • Author(s)
      Kobayashi Y, Uehara S, Koide M, Takahashi N
    • Journal Title

      Bonekey Rep

      Volume: 4 Pages: 713-713

    • DOI

      10.1038/bonekey.2015.82

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization.2015

    • Author(s)
      Kanemoto S, Kobayashi Y, Yamashita T, Miyamoto T, Cui M, Asada R, Cui X, Hino K, Kaneko M, Takai T, Matsuhisa K, Takahashi N, Imaizumi K.
    • Journal Title

      J Cell Sci

      Volume: 128 Pages: 4353-4365

    • DOI

      10.1242/jcs.176057

    • Related Report
      2015 Annual Research Report
    • 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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stability of mRNA influences steoporotic bone mass via CNOT32014

    • 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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noncanonical Wnt5a enhances Wnt/-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

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] VitaminD endocrine system and osteoclasts2014

    • Author(s)
      Takahashi N, Udagawa N, Suda T
    • Journal Title

      BoneKEy Reports

      Volume: 3 Pages: 495-495

    • DOI

      10.1038/bonekey.2013.229

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] oles of cathelicidins in inflammation and bone loss.2014

    • Author(s)
      Nakamichi Y, Horibe K, Udagawa N, Takahashi N
    • Journal Title

      Odontology

      Volume: 101 Issue: 2 Pages: 137-146

    • DOI

      10.1007/s10266-014-0167-0

    • Related Report
      2014 Annual Research Report
    • 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

    • Related Report
      2013 Annual Research Report
    • 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 Pages: 171-174

    • Related Report
      2013 Annual Research Report
    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-34 and CSF-1 similarities and differences2013

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of cathelicidin-related antimicrobial peptide in murine osteoclastogenesis2013

    • 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

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] いまデンティストリーに骨代謝がなぜ必要か2015

    • Author(s)
      高橋直之
    • Organizer
      Dentistry, Quo Vadis?
    • Place of Presentation
      星陵会館 (東京都千代田区)
    • Year and Date
      2015-12-06
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 破骨細胞研究から学んだこと2015

    • Author(s)
      高橋直之
    • Organizer
      平成27年度大阪歯科学会大会
    • Place of Presentation
      大阪歯科大学創立100周年記念館 (大阪市中央区)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 破骨細胞の研究からわかってきたこと2015

    • Author(s)
      高橋直之
    • Organizer
      歯科基礎平成27年度社員総会 生化学分野 分科会講演会
    • Place of Presentation
      日本歯科大学富士見ホール (東京都千代田区)
    • Year and Date
      2015-04-25
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 破骨細胞はどのような機序で骨組織に誘導される2014

    • Author(s)
      高橋直之
    • Organizer
      第45回京都骨・カルシウム代謝研究会
    • Place of Presentation
      ホテルグランヴィア京都、京都市 下京区
    • Year and Date
      2014-11-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 破骨細胞の分化と機能を調節するRANKL-RANKシグナ2014

    • Author(s)
      高橋直之
    • Organizer
      第一回日本骨免疫会議
    • Place of Presentation
      万国津梁館  名護市喜瀬
    • Year and Date
      2014-07-05
    • Related Report
      2014 Annual Research Report
    • Invited
  • [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
      長良川国際会議場  岐阜市長良福光
    • Year and Date
      2014-05-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [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
      星陵会館 千代田区永田町
    • Year and Date
      2013-12-07
    • Related Report
      2013 Annual Research Report
    • Invited
  • [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
    • Place of Presentation
      ホテルグランドシティー 豊島区東池袋
    • Year and Date
      2013-10-29
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-06-20   Modified: 2017-05-10  

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