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

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21515
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• Research Institution: The 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
• Keywords: 関節リウマチ

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.

Free Research Field

免疫学

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。