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Translational research on osteocrin for musculo-skeletal system

Research Project

Project/Area Number 18K16227
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKyoto University

Principal Investigator

Kanai Yugo  京都大学, 医学研究科, 客員研究員 (80802769)

Project Period (FY) 2018-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsOsteocrin / CNP / NPR-C / 骨伸長 / osteocrin / cnp / 内軟骨性骨化 / 骨伸長障害
Outline of Final Research Achievements

We have clarified that osteocrin promotes skeletal growth and its mechanisms are mediated by inhibiting NPR-C receptor, a clearance receptor of C-type natriuretic peptide (CNP), using osteocrin transgenic mice. Furthermore, we focused on neutral endopeptidase involving clearance of CNP. Administration of a neutral endopeptidase inhibitor promoted skeletal growth of wild-type mice as well as osteocrin. CNP has being developed as an agent of growth retardation and skeletal disorders. The present investigation provides important findings that molecules related to clearance of CNP has potential to be new therapeutic targets for them.

Academic Significance and Societal Importance of the Research Achievements

成長障害に対する治療薬は長らく成長ホルモン製剤に限られ、成長ホルモン抵抗性の疾患に対する治療が望まれてきた。このニーズに対してCNPの臨床応用が期待されており、関連する研究の社会的意義は大きいと思われる。最近ではCNPアナログ製剤の軟骨無形成症に対する臨床試験ではヒトにおける有効性も示され、CNPを軸とした新たな成長障害の治療開発が進む中で、CNPのクリアランスを制御修飾する薬剤の開発という観点での研究はこれまでなされていなかった。独創的かつ新たなアプローチによりこの領域の展開に寄与する点で、本研究の成果は学術的にも重要な位置を占めると考えられる。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2019 2018

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

  • [Journal Article] 特集 ホルモンによる骨代謝の制御 4.臓器連関から見たホルモンによる骨代謝調節(3)オステオクリンとC 型ナトリウム利尿ペプチド2019

    • Author(s)
      八十田 明宏、金井 有吾
    • Journal Title

      腎と骨代謝

      Volume: 32 Issue: 2 Pages: 158-163

    • DOI

      10.19020/KB.0000000203

    • ISSN
      0914-5265, 2433-2496
    • Year and Date
      2019-04-01
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Exogenous C-type natriuretic peptide therapy for impaired skeletal growth in a murine model of glucocorticoid treatment2019

    • Author(s)
      Ueda Yohei、Yasoda Akihiro、Hirota Keisho、Yamauchi Ichiro、Yamashita Takafumi、Kanai Yugo、Sakane Yoriko、Fujii Toshihito、Inagaki Nobuya
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1

    • DOI

      10.1038/s41598-019-44975-w

    • NAID

      120006775907

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Live imaging analysis of the growth plate in a murine long bone explanted culture system2018

    • Author(s)
      Hirota Keisho、Yasoda Akihiro、Kanai Yugo、Ueda Yohei、Yamauchi Ichiro、Yamashita Takafumi、Sakane Yoriko、Fujii Toshihito、Inagaki Nobuya
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-9

    • DOI

      10.1038/s41598-018-28742-x

    • NAID

      120006502590

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exogenous C-type natriuretic peptide restores normal growth and prevents early growth plate closure in its deficient rats2018

    • Author(s)
      Hirota Keisho、Furuya Mayumi、… Yasoda Akihiro、Inagaki Nobuya
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 9 Pages: e0204172-e0204172

    • DOI

      10.1371/journal.pone.0204172

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 循環血液中のオステオクリンはC型ナトリウム利尿ペプチドのクリアランスを阻害することにより骨伸長を促進する2018

    • Author(s)
      金井 有吾
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 循環血液中のオステオクリンはC型ナトリウム利尿ペプチドのクリアランスを阻害することにより骨伸長を促進する2018

    • Author(s)
      金井 有吾
    • Organizer
      第36回日本骨代謝学会学術集会
    • Related Report
      2018 Research-status Report
    • Invited

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Published: 2018-04-23   Modified: 2021-02-19  

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