CircRNA_0074834调控BMSCs成骨分化治疗绝经后骨质疏松症的作用机制研究

绝经后骨质疏松症（PMOP）在骨质疏松症中占比最大，显著增加中老年女性骨折风险。目前临床常用抗骨松药物作用机制多为抑制骨吸收，难以恢复已丢失的骨量。BMSCs成骨分化不足是PMOP发病的关键机制。前期工作中，我们发现PMOP患者BMSCs的circ_0074834表达明显降低。功能试验显示circ_0074834显著促进BMSCs成骨分化。通过生物信息学预测，circ_0074834可作为内源竞争性RNA（ceRNA）调控miRNA-942-5p活性。本研究将以临床资料为基础，明确circ_0074834的表达水平与PMOP的相关性；进一步阐明circ_0074834以ceRNA方式调控miR-942-5p及目的基因表达、从而调控BMSCs成骨分化的具体机制，并通过体内实验验证circ_0074834对PMOP的治疗作用。本研究可深化对PMOP发病机制的了解，为PMOP的治疗提供新靶点。

Being the most common subtype of osteoporosis, PMOP significantly increases the risk of bone fracture in women. Most of the anti-osteoporosis medicine work through inhibiting bone resorption instead of promoting bone formation. Insufficient osteogenic differentiation of BMSCs plays a key role in the pathogenesis of PMOP. In our previous work, we found that the expression of circ_0074834 was significantly decreased in PMOP patients. Function test demonstrated that circ_0074834 promoted the osteogenic differentiation of BMSCs significantly. By bioinformatics methods and double-luciferase reporter assay, we found that circ_0074834 functions as a ceRNA for miRNA-942-5p to regulate the expression of target genes. Based on clinical data, this study will verify the relationship between the expression of circ_0074834 with PMOP. Our study will further explore the mechanisms of the regulation of miR-942-5p and target genes by circ_0074834. Moreover, we will detect the therapeutic effect of circ_0074834 on PMOP in vivo. This study would help us dig further into the pathogenesis of PMOP and provide new therapeutic target for PMOP.