Study on the molecular mechanism of prevention of steroid-induced osteonecrosis of the femur by intravenous administration of mesenchymal stem cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K18510
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa Medical University
• Principal Investigator: SHIMASAKI Miyako 金沢医科大学, 医学部, 講師 (00440511)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 骨髄由来間葉系幹細胞(MSC9 / 酸化ストレス / 低酸素 / 抗炎症作用 / 分化能

Outline of Final Research Achievements

1. Ischemic hypoxia and mitochondrial damage are the main causes of steroid-induced osteonecrosis of the femur. Maintenance of mitochondrial function in osteocytes is essential for the prevention of osteonecrosis. Development of osteocyte necrosis was suppressed by mitochondrial transcription factor A (TFAM). TFAM has a protective effect on cell necrosis and prevents osteonecrosis in cultured osteocytes. 2.In order to demonstrate the efficacy of mesenchymal stem cells (MSCs) in prevention and treatment by tissue repair, we investigated the stress tolerance of MSCs against steroid administration and hypoxic stress. The stress resistance of MSCs to steroid administration and hypoxic stress was investigated. MSCs maintained mitochondrial function under stress and suppressed oxidative stress.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

1.TFAM はミトコンドリアの機能維持、酸化傷害の抑制、ATP 産生の維持において重要であることが示された。ミトコンドリア損傷の予防は、骨細胞壊死の進行を減少させる事が効果的であるため、酸化傷害の抑制、ATP 産生の維持に関与するTFAMは骨壊死予防における治療法に応用できる可能性が高い。2.デキサメタゾンおよび低酸素によるストレスに曝されたM間葉系幹細胞(BM-MSC)はミトコンドリア機能を維持し、酸化ストレスの抑制を示した。骨細胞死を引き起こすのに十分なストレスのかかる条件下でもMSCは機能は維持し、骨壊死に対し骨内移植における予防および治療戦略が有望である可能性が示唆された。