LncRNA Tmem235通过调控BIRC5抑制BMSCs凋亡对修复早期激素性股骨头坏死的作用和机制

骨髓间充质干细胞（BMSCs）已用于治疗早期激素性股骨头坏死（SONFH）。但大量BMSCs在骨坏死区缺氧性凋亡，使其疗效受限。需寻找干预策略。我们的芯片和预实验结果表明LncRNA Tmem235可抑制BMSCs缺氧性凋亡，生信分析提示miR-34a-3p/BIRC5可能是LncRNA Tmem235的下游调控靶点。据此，我们推测：LncRNA Tmem235通过调控miR-34a-3p/BIRC5抑制BMSCs缺氧性凋亡，可提高BMSCs的移植疗效。本项目通过干预LncRNA Tmem235、miR-34a-3p和BIRC5，研究LncRNA Tmem235抑制BMSCs缺氧性凋亡的机制，评估LncRNA Tmem235抑制BMSCs缺氧性凋亡对修复早期SONFH的作用。本项目创新点在于发现LncRNA Tmem235抗缺氧性凋亡的作用及其调控机制，为提高BMSCs移植疗效探求新思路。

Bone marrow mesenchymal stem cells (BMSCs) have been used to treat early steroid-induced osteonecrosis of the femoral head (SONFH). However, a large number of BMSCs undergo hypoxia-induced apoptosis in the osteonecrotic area, which limits the therapeutic efficacy. This matter needs further intervention. Our microarray and pilot experimental results indicated that the long non-coding RNA (LncRNA) Tmem235 inhibited hypoxia-induced apoptosis of BMSCs. Bioinformatics analysis suggests that microRNA-34a-3p (miR-34a-3p)/baculoviral IAP repeat containing 5 (BIRC5) may be the downstream regulatory target of LncRNA Tmem235. Therefore, we hypothesize that LncRNA Tmem235 may inhibit hypoxia-induced apoptosis of BMSCs by regulating miR-34a-3p/BIRC5, which may improve the transplantation efficacy of BMSCs. In this study, we plan to use intervention with LncRNA Tmem235, miR-34a-3p, and BIRC5 to investigate the mechanism by which LncRNA Tmem235 inhibits the hypoxia-induced apoptosis of BMSCs and evaluate the effect of LncRNA Tmem235 inhibition of hypoxia-induced apoptosis of BMSCs on the repair of early SONFH. The innovation of this study is that we will identify both the role of LncRNA Tmem235 in hypoxia-induced apoptosis and its regulatory mechanism, which will provide new ideas for improving the efficacy of BMSCs transplantation.