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Analysis on the pharmacological mechanism of W9 peptide and development for the novel drug based on the strong potential for chondrocyte differentiation

Research Project

Project/Area Number 18H02918
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionThe University of Tokyo

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 本間 雅  東京大学, 医学部附属病院, 講師 (60401072)
Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Keywords軟骨代謝 / Wペプチド / 細胞内シグナル / 抗体創薬 / W9ペプチド / 軟骨細胞
Outline of Final Research Achievements

The purpose of this study is to elucidate the pharmacological target of W9 peptide, which shows the potential of chondrogenesis. At first, we searched binding target of W9 peptide using avidin-streptavidin pulldown method, and a couple of cell surface proteins were identified. Therefore, we performed knockdown and knockout experiment in ATDC5, a chondrocyte like cell derived from mice, to examine the involvement of these proteins. Furthermore, downstream signaling pathways in W9-stimulated ATDC5 cells were confirmed by phosphorylated proteomics analysis. Based on these analyses, we designed bispecific antibodies to crosslink W9 target proteins, which may mimic biotin-labelled W9 peptide, and evaluate pharmacological effects.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症などの軟骨関連疾患は、健康寿命を縮める主な要因の一つであり、超高齢化社会へと進展している現在では克服すべき課題となっている。ビオチン修飾を施したW9ペプチドは、軟骨細胞分化に関わる他の分子と比較しても強い活性を有しており、これを選択的に入力できる抗体医薬の開発に成功すれば、臨床的に非常に大きな意義を持つ。また、得られた抗体分子の構造最適化に関する知見は、他の疾患治療薬の開発にも活かせることが期待され、今後の研究活動の基盤になるものと考えている。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (23 results)

All 2021 2020 2019 2018 Other

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (11 results) (of which Int'l Joint Research: 5 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] RANKL as a key figure in bridging between the bone and immune system: Its physiological functions and potential as a pharmacological target2021

    • Author(s)
      Honma Masashi、Ikebuchi Yuki、Suzuki Hiroshi
    • Journal Title

      Pharmacology & Therapeutics

      Volume: 218 Pages: 107682-107682

    • DOI

      10.1016/j.pharmthera.2020.107682

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of RANKL delivery to the osteoclast precursor cell surface2020

    • Author(s)
      Honma Masashi、Ikebuchi Yuki、Suzuki Hiroshi
    • Journal Title

      Journal of Bone and Mineral Metabolism

      Volume: 39 Issue: 1 Pages: 27-33

    • DOI

      10.1007/s00774-020-01157-3

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RANKL逆シグナルによる骨代謝制御2019

    • Author(s)
      本間雅、池淵祐樹、鈴木洋史
    • Journal Title

      生化学

      Volume: 91 Pages: 529-532

    • Related Report
      2019 Annual Research Report
  • [Journal Article] カップリング・シグナル受容分子としてのRANKL2019

    • Author(s)
      本間雅、池淵祐樹、鈴木洋史
    • Journal Title

      THE BONE

      Volume: 33 Pages: 57-61

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 骨吸収と骨形成のカップリングにおけるRANKL逆シグナルの関与2019

    • Author(s)
      本間雅、池淵祐樹、鈴木洋史
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 71 Pages: 608-614

    • NAID

      40021933906

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 骨形成・吸収におけるRANKリガンドシグナルの新たな役割2019

    • Author(s)
      池淵祐樹、本間雅、鈴木洋史
    • Journal Title

      血液内科

      Volume: 79 Pages: 100-105

    • NAID

      40021979045

    • Related Report
      2019 Annual Research Report
  • [Journal Article] RANKL逆シグナル経路を標的とした新たな創薬の可能性2019

    • Author(s)
      本間雅、池淵祐樹、鈴木洋史
    • Journal Title

      BIO Clinica

      Volume: 34 Pages: 773-777

    • Related Report
      2019 Annual Research Report
  • [Journal Article] The clustering-induction of RANKL molecules could stimulate early osteroblast differentiation2019

    • Author(s)
      E. Sone, D. Noshiro, Y. Ikebuchi, M. Nakagawa, M. Khan, Y. Tamura, M. Ikeda, M. Oki, R. Murali, T. Fujimori, T. Yoda, M. Honma, H. Suzuki, T. Ando, and K. Aoki
    • Journal Title

      Biophys. Biochem. Res. Commun.

      Volume: 509 Issue: 2 Pages: 435-440

    • DOI

      10.1016/j.bbrc.2018.12.093

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Coupling of bone resorption and formation by RANKL reverse signalling.2018

    • Author(s)
      Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H
    • Journal Title

      Nature

      Volume: 561 Issue: 7722 Pages: 195-200

    • DOI

      10.1038/s41586-018-0482-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RANKL結合ペプチドによる骨形成促進メカニズムの検討2018

    • Author(s)
      曽根絵梨、Masud Khan、能代大輔、池淵祐樹、本間雅、田村幸彦、菅森泰隆、鈴木洋史、宇田川信之、青木和宏
    • Journal Title

      日本骨形態計測学会雑誌

      Volume: 28

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] RANKL逆シグナルによる骨吸収と骨形成の共役2018

    • Author(s)
      本間雅, 池淵祐樹
    • Journal Title

      First Author's

      Volume: - Pages: 095

    • DOI

      10.7875/first.author.2018.095

    • Related Report
      2018 Annual Research Report
    • Open Access
  • [Presentation] RANK-RANKLによる骨代謝制御機構の解析と新たな骨粗鬆症治療薬の可能性2020

    • Author(s)
      池淵祐樹
    • Organizer
      埼玉医科大学 卒後教育委員会後援学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Develoment of a novel biologic agent for treating RA2019

    • Author(s)
      Honma M., Kurata R., Ikebuchi Y., Kariya Y., Suzuki H.
    • Organizer
      European Calcified Tissue Society Congress 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨吸収と骨形成のカップリングにおけるRANKL逆シグナルの寄与2019

    • Author(s)
      池淵祐樹
    • Organizer
      第5回日本骨免疫学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] RANK-RANKLを介したカップリング制御機構と新たな創薬の可能性2019

    • Author(s)
      池淵祐樹
    • Organizer
      第37回日本骨代謝学会学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 関節リウマチに関する新規バイオロジクスの創製検討2018

    • Author(s)
      藏田玲美、本間雅、池淵祐樹、苅谷嘉明、鈴木洋史
    • Organizer
      日本薬剤学会第33年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] A stimulatory mechanism of RANKL-binding peptide on osteoblast differentiation2018

    • Author(s)
      Sone, E.、Noshiro, D.、Ikebuchi, Y.、Khan, M.、Sugamori, Y.、Tamura, Y.、Yoda, T.、Honma, M.、Aoki, K.
    • Organizer
      32nd IADR Southeast Asian Division Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 骨芽細胞に発現するRANKLはカップリング・シグナルを受容する2018

    • Author(s)
      池淵祐樹、本間雅、苅谷嘉明、鈴木洋史
    • Organizer
      第40回 生体膜と薬物の相互作用シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Osteoblastic RANKL acts as an osteogenic signal acceptor recognizing vesicular RANK secreted from osteoclasts2018

    • Author(s)
      Honma, M.、Ikebuchi, Y.、Suzuki, H.
    • Organizer
      ASEMV 2018 Annual Meeting
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Osteoblastic RANKL acts as an osteogenic signal acceptor for vesicular RANK derived from maturing osteoclasts.2018

    • Author(s)
      Honma, M.、Ikebuchi, Y.、Kariya, Y.、Suzuki, H.
    • Organizer
      AAPS PharmSci 360
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of a novel chimeric protein construct aiming to improve therapeutic efficacy against rheumatoid arthritis2018

    • Author(s)
      Kurata, R.、Honma, M.、Ikebuchi, Y.、Kariya, Y.、Suzuki, H.
    • Organizer
      AAPS PharmSci 360
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RANKL逆シグナルによる骨吸収と骨形成のカップリング2018

    • Author(s)
      池淵祐樹
    • Organizer
      第21回 骨代謝研究会
    • Related Report
      2018 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

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

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report 2019 Annual Research Report 2018 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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