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Elucidation of bone destruction in rheumatoid arthritis and development of novel therapies

Research Project

Project/Area Number 20K21515
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 49:Pathology, infection/immunology, and related fields
Research InstitutionThe University of Tokyo

Principal Investigator

Komatsu Noriko  東京大学, 大学院医学系研究科(医学部), 助教 (20553358)

Project Period (FY) 2020-07-30 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords関節リウマチ / 関越リウマチ
Outline of Research at the Start

関節リウマチでは、関節部位のみならず関節外の部位においても骨吸収の亢進がみとめられる。骨折のリスクの向上やQOLの低下につながるため、そのメカニズムの理解と治療法の開発は喫緊の課題である。しかしながらその機構は未だ不明な点が多く、完全な治療法は存在しない。既存製剤が抱える免疫抑制による副作用や無効例の存在、関節外の部位の骨量低下を制御できないという問題を克服する画期的な治療法の開発が喫緊である。本研究では申請者の独自の知見に基づき、新規悪玉細胞サブセットを同定し関節リウマチの骨破壊の病態解明と革新的な骨破壊抑制法の開発を目指す。

Outline of Final Research Achievements

In rheumatoid arthritis, not only joint erosion but also periarticular bone loss and systemic osteoporosis are observed, while the mechanism of periarticular bone loss and systemic osteoporosis remains largely unknown. In this study, we found that the number of bone marrow plasma cells increases under arthritic conditions and they induce periarticular bone loss by expressing the osteoclast differentiation factor, RANKL. In addition, we clarified that synovial fibroblasts are major RANKL expressing cells which induce joint erosion. This study highlights the importance of plasma-cell RANKL in periarticular bone loss in arthritis and provides mechanistic insight into the manifestation of bone lesion induced by autoimmunity.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチでは関節破壊以外にも関節近傍や全身性に骨粗鬆症が起きる。骨粗鬆症は関節リウマチ患者の骨折リスクを上げ、生活の質を下げるが、これまでの治療法では関節破壊の進行を抑制できても骨粗鬆症は十分に抑制できないという問題があった。本研究においてマウスモデルを使用して明らかとなった傍関節性骨粗鬆症や関節破壊のメカニズムは関節リウマチの骨破壊の治療法の開発に貢献すると考えられる。

Report

(3 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • Research Products

    (20 results)

All 2022 2021 2020

All Journal Article (4 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (12 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results) Book (4 results)

  • [Journal Article] Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis2021

    • Author(s)
      Komatsu N, Win S, Yan M, Huynh CN N, Sawa S, Tsukasaki M, Terashima A, Pluemsakunthai W, Kollias G, Nakashima T and Takayanagi H
    • Journal Title

      J Clin Invest.

      Volume: 131 Issue: 6 Pages: 1-8

    • DOI

      10.1172/jci143060

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] tepwise cell fate decision pathways during osteoclastogenesis at single-cell resolution.2021

    • Author(s)
      Tsukasaki M, Huynh NC, Okamoto K, Muro R, Terashima A, Kurikawa Y, Komatsu N, Pluemsakunthai W, Nitta T, Abe T, Kiyonari H, Okamura T, Sakai M, Matsukawa T, Matsumoto M, Kobayashi Y, Penninger JM, Takayanagi H
    • Journal Title

      Nat Metab

      Volume: 2 Issue: 12 Pages: 1382-1390

    • DOI

      10.1038/s42255-020-00318-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] OPG Production Matters Where It Happened.2020

    • Author(s)
      Tsukasaki M, Asano T, Muro R, Huynh NC, Komatsu N, Okamoto K, Nakano K, Okamura T, Nitta T, Takayanagi H
    • Journal Title

      Cell Rep

      Volume: 32 Issue: 10 Pages: 1-10

    • DOI

      10.1016/j.celrep.2020.108124

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells2020

    • Author(s)
      Daisuke Takahashi, Naomi Hoshina, Yuma Kabumoto, Yuichi Maeda, Akari Suzuki, Hiyori Tanabe, Junya Isobe, Takahiro Yamada, Kisara Muroi, Yuto Yanagisawa, Atsuo Nakamura, ... Koji Hase
    • Journal Title

      EBioMedicine

      Volume: 58 Pages: 102913-102913

    • DOI

      10.1016/j.ebiom.2020.102913

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 自己免疫性関節炎の 傍関節性骨粗鬆症の誘導機構2022

    • Author(s)
      小松紀子 Yan Minglu 塚崎雅之 高柳広
    • Organizer
      日本骨免疫学会 ウィンタースクール
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自己免疫性関節炎における 破骨細胞誘導細胞の同定2022

    • Author(s)
      小松紀子 高柳広
    • Organizer
      日本薬学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自己免疫性関節炎における骨破壊誘導細胞の同定2022

    • Author(s)
      小松紀子
    • Organizer
      北海道大学 免疫代謝内科学セミナー
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 形質細胞による骨破壊誘導機構2022

    • Author(s)
      小松紀子
    • Organizer
      東京免疫フォーラム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 自己免疫性関節炎の骨破壊における破骨細胞誘導細胞の同定2021

    • Author(s)
      小松紀子 高柳広
    • Organizer
      日本リウマチ学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自己免疫性関節炎の骨破壊における破骨細胞誘導細胞の同定2021

    • Author(s)
      小松紀子 高柳広
    • Organizer
      日本炎症再生・医学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 炎症による骨代謝制御機構の解明2021

    • Author(s)
      小松紀子
    • Organizer
      日本骨代謝学会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Plasma cells promote osteoclastogenesis and periarticular bone loss in autoimmune arthritis2021

    • Author(s)
      小松紀子
    • Organizer
      日本免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 形質細胞が自己免疫性関節炎の傍関節性骨粗鬆症を誘導する2021

    • Author(s)
      小松紀子
    • Organizer
      ベーシックリサーチカンファレンス
    • Related Report
      2021 Annual Research Report
  • [Presentation] Identification of osteoclast inducer cells in bone destruction in autoimmune arthritis2021

    • Author(s)
      Noriko Komatsu
    • Organizer
      Japan Bone Academy 2021
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A distal enhancer regulates RANKL expression in synovial fibroblasts in arthritis2021

    • Author(s)
      Minglu Yan, Noriko Komatsu, Ryunosuke Muro, Hiroyuki Takaba, Takeshi Nitta, Kazuo Okamoto, Masayuki Tsukasaki, Hiroshi Takayanagi
    • Organizer
      日本免疫学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 自己免疫性関節炎における細胞特異的RANKL発現の病理的意義2020

    • Author(s)
      小松紀子、高柳広
    • Organizer
      日本リウマチ学会
    • Related Report
      2020 Research-status Report
  • [Book] 骨・軟骨・筋科学Update2021

    • Author(s)
      小松紀子
    • Total Pages
      3
    • Publisher
      国際医学出版
    • Related Report
      2021 Annual Research Report
  • [Book] 炎症と免疫2021

    • Author(s)
      小松紀子
    • Total Pages
      3
    • Publisher
      先端医学社
    • Related Report
      2021 Annual Research Report
  • [Book] Bio Clinica2020

    • Author(s)
      小松紀子
    • Total Pages
      5
    • Publisher
      北隆館
    • Related Report
      2020 Research-status Report
  • [Book] Encyclopedia of Bone Biology2020

    • Author(s)
      Komatsu Noriko, and Takayanagi Hiroshi
    • Total Pages
      8
    • Publisher
      Academic press
    • Related Report
      2020 Research-status Report

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Published: 2020-08-03   Modified: 2023-01-30  

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