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Analysis on the regulatory mechanism of sclerostin expression coupled with RANKL-reverse signaling

Research Project

Project/Area Number 25670632
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

IKEBUCHI Yuki  東京大学, 医学部附属病院, 助教 (20645725)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords骨細胞 / 骨代謝カップリング / 骨カップリング / 細胞分化制御
Outline of Final Research Achievements

Regulatory mechanisms of SOST expression, which is a secreted protein from osteocytes and suppresses bone formation, still remain unclear. We focused on "RANKL reverse signaling" based on RANKL function as a receptor for RANK. At first, we established optimized in vitro assay methods for evaluating osteocyte functions. During 3-dimensional culture composed of type-I collagen and matrigel, osteocytes kept the characteristic features of gene expression and its cell shape over 7 days. Using this novel culture conditions, we examined the effect of RANKL reverse signaling on SOST expression in osteocytes. As a result, activating RANKL reverse signaling resulted in the significant elevation of SOST expression, as well as the ratio of RANKL to OPG expression. Moreover, these effects were also confirmed in mouse in vivo model. Consequently, RANKL reverse signaling in osteocytes may contribute to the efficient bone coupling between bone resorption and formation.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (5 results)

All 2014 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) Remarks (1 results)

  • [Journal Article] Establishment of optimized in vitro assay methods for evaluating osteocyte functions.2014

    • Author(s)
      Honma M, Ikebuchi Y, Kariya Y, Suzuki H.
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: [Epub ahead of print]

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regulatory mechanisms of RANKL presentation to osteoclast precursors2014

    • Author(s)
      Masashi Honma, Yuki Ikebuchi, Yoshiaki Kariya, Hiroshi Suzuki
    • Journal Title

      Current Osteoporosis Reports

      Volume: 12(1) Issue: 1 Pages: 115-120

    • DOI

      10.1007/s11914-014-0189-0

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Analysis on the regulatory mechanisms of osteocytic RANKL presentation to osteoclast precursors.2014

    • Author(s)
      Yuki Ikebuchi
    • Organizer
      第8回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      熊本
    • Year and Date
      2014-11-15 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 成熟破骨細胞形成における骨細胞RANKL提示機構の解析2014

    • Author(s)
      池淵祐樹
    • Organizer
      新学術領域「統合的多階層生体機能学領域の確立とその応用」若手ワークショップ2014
    • Place of Presentation
      熱海
    • Year and Date
      2014-09-21 – 2014-09-23
    • Related Report
      2014 Annual Research Report
  • [Remarks] 東京大学医学部附属病院薬剤部試験研究室/臨床薬物動態学教室

    • URL

      http://plaza.umin.ac.jp/~todaiyak/

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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