Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Orthopedic Laboratory of Chongqing Medical University, Chongqing, People's Republic of China.
Stem Cells. 2023 Jul 14;41(7):711-723. doi: 10.1093/stmcls/sxad038.
Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.
增强间充质干细胞(MSCs)的成脂分化被认为是导致激素性股骨头坏死(SOFNH)的一个主要危险因素。在这个过程中,microRNAs 的作用引起了人们的兴趣。SONFH 患者和大鼠模型的股骨头骨组织中 miR-486-5p 的表达明显下调。本研究旨在揭示 miR-486-5p 对 MSCs 成脂分化和 SONFH 进展的作用。本研究表明,miR-486-5p 通过抑制有丝分裂克隆扩张(MCE),可显著抑制 3T3-L1 细胞的成脂分化。miR-486-5p 介导的 TBX2 减少引起的 P21 表达上调,是抑制 MCE 的原因。此外,miR-486-5p 可有效抑制激素诱导的股骨头脂肪形成,并在大鼠模型中预防 SONFH 进展。鉴于 miR-486-5p 对抑制成脂作用的强大效果,它似乎是治疗 SONFH 的一个有前途的靶点。