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Roles of an atypical Wnt receptor, Ryk, for bone remodeling(Fostering Joint International Research)

Research Project

Project/Area Number 15KK0356
Research Category

Fund for the Promotion of Joint International Research (Fostering Joint International Research)

Allocation TypeMulti-year Fund
Research Field Functional basic dentistry
Research InstitutionMatsumoto Dental University

Principal Investigator

Nakamichi Yuko  松本歯科大学, 総合歯科医学研究所, 講師 (20350829)

Research Collaborator Major Michael Ben  University of North Carolina at Chapel Hill, Lineberger Cancer Center, Associate Professor
Udagawa Nobuyuki  松本歯科大学, 歯学部, 教授
Project Period (FY) 2016 – 2018
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Keywordsプロテオーム / ゲノム / シグナル伝達
Outline of Final Research Achievements

WNT signaling controls myriad biological processes throughout life of all animals. Ryk is a member of the Wnt receptors and does not belong to the conventional classification of the Wnt signal transduction. Little is known about its mechanism of action. Ryk may be involved in Wnt-regulated processes in bone remodeling. In this study, we elucidated roles of Ryk for bone and mineral metabolism by using Ryk conditional KO (cKO) mice lines that are established in our laboratory. Using two mesenchymal-specific Ryk cKO mice, we confirmed that Ryk enhances bone formation. In addition to the analysis of Ryk cKO mice, we tried to identify osteotropic downstream molecules of Wnt3a (one of the Ryk ligands), utilizing the analysis platform developed by the oversea collaborator, the Major laboratory (UNC-CH). To this end, we set up a functional genomic screening with a gain-of-function approach (called Crispr-A) and developed a sensitive reporter system. We also performed Phospho-MS analysis.

Academic Significance and Societal Importance of the Research Achievements

最近、Wntシグナルが活性化している悪性腫瘍において、抗腫瘍免疫活性がWntシグナルにより抑制されているという報告が多数存在する。これはRyk が、癌治療の有望な分子標
的であることを示す。本研究ではゲノムワイドスクリーニングの系の立ち上げに成功した。今後、Ryk シグナルのエフェクター分子が同定されれば、基礎生物学のブレイクスルーとなる。このエフェクター分子は骨形成促進薬となり得るばかりか、骨や神経の再生医療、がん治療、および口蓋裂などの歯科領域治療における分子標的にもなる可能性がある。将来的には、この分子標的を利用した新規治療法の開発がもたらされることが期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2019 2018 2017

All Int'l Joint Research (1 results) Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Int'l Joint Research] ノースカロライナ大学チャペルヒル校(米国)2017

    • Year and Date
      2017-09-05
    • Related Report
      2018 Annual Research Report
  • [Journal Article] WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop2019

    • Author(s)
      Agajanian MJ, Walker MP, Axtman AD, Ruela-de-Sousa RR, Serafin DS, Rabinowitz AD, Graham DM, Ryan MB, Tamir T, Nakamichi Y, Gammons MV, Bennett JM, Counago RM, Drewry DH, Elkins JM, Gileadi C, Gileadi O, Godoi PH, Kapadia N, Muller, Santiago A, Sorrell FJ, Wells CI, Fedorov O, Willson TM, Zuercher WJ, Major MB.
    • Journal Title

      Cell Reports

      Volume: 26 Issue: 1 Pages: 79-93.e8

    • DOI

      10.1016/j.celrep.2018.12.023

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Mechanisms involved in bone resorption regulated by vitamin D2018

    • Author(s)
      Nakamichi Yuko、Udagawa Nobuyuki、Suda Tatsuo、Takahashi Naoyuki
    • Journal Title

      The Journal of Steroid Biochemistry and Molecular Biology

      Volume: 177 Pages: 70-76

    • DOI

      10.1016/j.jsbmb.2017.11.005

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chapter 18 Osteoclastogenesis and Vitamin D2018

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

      Vitamin D (Fourth Edition)

      Volume: 1 Pages: 309-317

    • DOI

      10.1016/b978-0-12-809965-0.00018-5

    • ISBN
      9780128099650
    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The W9 peptide directly stimulates osteoblast differentiation via RANKL signaling.2017

    • Author(s)
      Nakamura M, Nakamichi Y, Mizoguchi T, Koide M, Yamashita T, Ara T, Nakamura H, Penninger JM, Furuya Y, Yasuda H, and Udagawa N
    • Journal Title

      Journal of Oral Biosciences

      Volume: 59 Issue: 3 Pages: 146-151

    • DOI

      10.1016/j.job.2017.05.001

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] VDR in osteoblast-lineage cells primarily mediates vitamin D treatment-iInduced increase in bone mass by suppressing bone resorption.2017

    • Author(s)
      Nakamichi Y, Udagawa N, Horibe K, Mizoguchi T, Yamamoto Y, Nakamura T, Hosoya A, Kato S, Suda T, Takahashi N
    • Journal Title

      J Bone Miner Res

      Volume: 32 Issue: 6 Pages: 1297-1308

    • DOI

      10.1002/jbmr.3096

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Roles of VDR in osteoblasts and osteoclasts for vitamin D-induced increase in bone mass:2017

    • Author(s)
      Nakamichi Y
    • Organizer
      Bone Biology Forum (第14回)
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨ミネラル代謝における骨芽細胞および骨細胞の VDR の役割2017

    • Author(s)
      中道裕子
    • Organizer
      Neo Vitamin D Workshop (第3回)
    • Related Report
      2017 Research-status Report
  • [Presentation] 骨ミネラル代謝における骨芽細胞/骨細胞のVDRの役割2017

    • Author(s)
      中道裕子
    • Organizer
      25(OH)Dを考える会 (第4回)
    • Related Report
      2017 Research-status Report
    • Invited

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Published: 2016-10-04   Modified: 2020-03-30  

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