New prevention of steroid-induced osteonecrosis with mitochondrial transcription factor A

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K18511
• 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: UEDA Shusuke 金沢医科大学, 医学部, 助教 (10759583)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: ステロイド関連大腿骨頭壊死症 / ミトコンドリア転写因子A / TFAM knockdown / 酸化障害 / 骨髄由来間葉系幹細胞 / ミトコンドリア障害 / 骨細胞死

Outline of Final Research Achievements

Oxidative stress has been implicated as one of the causes of glucocorticoid-associated osteonecrosis of the femoral head. We have confirmed that oxidative stress is also expressed at the cellular level by creating an equivalent environment for cultured osteocytic cells. We also focused on mitochondrial transcription factor A (TFAM), which is susceptible to oxidative damage. By knocking down TFAM, we confirmed that mitochondria were not preserved, and mitochondrial function could not be maintained. Furthermore, the addition of TFAM to cultured osteocytes significantly reduced oxidative damage and osteocytic cell death in an environment equivalent to osteonecrosis. This suggests the involvement of mitochondrial dysfunction in glucocorticoid-associated osteonecrosis of the femoral head.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

ステロイド関連大腿骨頭壊死症は難治性疾患とされており、その機序解明や予防法の確立は非常に重要である。また、骨壊死が発生した場合不可逆性であり、骨頭の圧壊が発生してしまうと外科的な処置が必要になる。本研究は骨壊死においてミトコンドリアの関与を示しており、ミトコンドリアを保護することで骨壊死の治療や予防に期待できる。