Identification and visualization of pathological osteoclasts in arthritis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23967
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0902:General internal medicine and related fields
• Research Institution: Osaka University
• Principal Investigator: Hasegawa Tetsuo 大阪大学, 医学系研究科, 招へい教員 (30773048)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 破骨細胞 / 関節リウマチ / 生体イメージング

Outline of Final Research Achievements

Osteoclasts are multinucleated cells with unique bone-destroying capacity. They play key roles in maintaining homeostatic bone remodeling inside the bone marrow (BM), while they are also involved in pathological bone destruction in arthritis. However, the difference between these osteoclasts in the two tissue settings have not been clarified. Here, we used two-photon microscopy to directly visualize the mature osteoclasts both in the BM and pannus-bone interface. This showed that pathological osteoclasts are actively resorbing the bone matrix in the tiny resorption pits without migrating on the bone surface. This contrasts with the physiological osteoclasts in the BM, which are in close contact with osteoblasts and slowly migrate on the bone surface. These results imply that the manner of bone resorption differs between the osteoclast populations in the two tissues, and this system can serve as a platform for exploring the dynamics of osteoclasts within the synovial microenvironment.

Free Research Field

リウマチ膠原病

Academic Significance and Societal Importance of the Research Achievements

関節リウマチは関節の慢性的な炎症をきたす代表的な自己免疫疾患で、最終的に「破骨細胞」と呼ばれる細胞が骨を破壊することで関節の機能を大きく低下させます。近年、関節リウマチに対する治療薬は大きな進歩を遂げた一方、いまだにいずれの治療薬にも反応しない難治性の患者さんが存在します。本研究により、関節破壊を惹起する病的な破骨細胞の特徴やその骨破壊のメカニズムが詳細に解析されることで、病的な破骨細胞のみを標的とした新規薬剤の開発につながることが期待されます。