Elucidation of bone destruction in rheumatoid arthritis and development of novel therapies
| Project/Area Number |
20K21515
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 49:Pathology, infection/immunology, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Komatsu Noriko 東京大学, 大学院医学系研究科(医学部), 助教 (20553358)
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| 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)
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| Keywords | 関節リウマチ / 関越リウマチ |
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| 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。
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| 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.
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| 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。
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Report
(3 results)
Research Products
(20 results)
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[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
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Journal Title
Nat Metab
Volume: 2
Issue: 12
Pages: 1382-1390
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[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
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Journal Title
EBioMedicine
Volume: 58
Pages: 102913-102913
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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