Analysis of KDM1A-mediated intercellular network in inflammatory arthritis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K09298
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kyoto University
• Principal Investigator: Murata Koichi 京都大学, 医学研究科, 特定助教 (60806793)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 関節リウマチ / 破骨細胞 / 筋細胞 / サルコペニア

Outline of Final Research Achievements

KDM1A regulated inflammatory pathways, hypoxic pathways, and cell cycle pathways in osteoclast differentiation. Furthermore, higher expression of KDM1A was observed in RA synovial tissues than in OA tissue. TNF stimulation enhanced KDM1A expression in macrophage. When KDM1A inhibitor was administered to inflammatory arthritis model mice, it suppressed bone erosion and resorption caused by synovitis without suppressing arthritis. Next, the role of KDM1A in improving sarcopenia during the recovery phase of the arthritis model was investigated. When KDM1A inhibitor was administered to the mouse arthritis model, inhibition by KDM1A did not significantly restore muscle mass or strength in grip strength, or endurance on a treadmill. No improvement was observed in the cross-sectional area of tibialis anterior muscle in histopathology sections.

Free Research Field

骨代謝

Academic Significance and Societal Importance of the Research Achievements

現在の骨吸収抑制薬は全身に作用するため、長期的な骨代謝抑制の問題があり、炎症局所での骨吸収抑制薬の開発が望まれる。KDM1A阻害は関節炎において炎症を抑制させずに、骨破壊を抑制する。またKDM1A阻害薬はその代謝経路から炎症性関節炎における炎症部位特異的な新たな骨破壊抑制薬となり得る可能性がある。しかし、炎症性関節炎におけるサルコペニア回復に対する効果は認めない。