Postmenopausal osteoporosis, the most common type of primary osteoporosis, poses a significant threat to women's health worldwide. However, detailed molecular mechanism and therapeutic strategy for postmenopausal osteoporosis remain insufficient. Increasing evidence suggests that microRNAs contributed to the pathogenesis of osteoporosis and could be considered as potential therapeutic targets. In this study, we found that miR-151a-3p was upregulated in osteoporosis samples. Experiments in MC3T3-E1 cells indicated that miR-151a-3p significantly inhibited cell viability and promoted lactate dehydrogenase release, as well as increased RANKL/OPG ratio and decreased Runx2 and BMP2 expressions. SOCS5 was identified as a direct target gene of miR-151a-3p, which was confirmed by luciferase reporter assay. Moreover, an inverse correlation between miR-151a-3p and SOCS5 was observed in osteoporosis femurs. In addition, JAK2/STAT3 pathway was found to be involved in the progress of osteoporosis mediated by miR-151a-3p-SOCS5 axis. In vivo, ovariectomized (OVX) rat model was established to simulate postmenopausal osteoporosis. The results revealed that miR-151a-3p significantly decreased the bone mineral density and biomechanical parameters of femurs in OVX rats by targeting SOCS5, and that JAK2/STAT3 pathway is a downstream target of miR-151a-3p-SOCS5 axis in OVX rats. In conclusion, our findings suggested that miR-151a-3p contributed to the pathogenesis of postmenopausal osteoporosis, and promoted its progress by targeting SOCS5 and activating JAK2/STAT3 signaling. Thus, anti-miR-151a-3p could be a potential therapeutic strategy for postmenopausal osteoporosis.

中文翻译：

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MiR-151a-3p通过靶向SOCS5和激活JAK2 / STAT3信号传导来促进绝经后骨质疏松症。

绝经后骨质疏松症是最常见的原发性骨质疏松症，对全世界妇女的健康构成重大威胁。然而，绝经后骨质疏松症的详细分子机制和治疗策略仍然不足。越来越多的证据表明，microRNA促进了骨质疏松症的发病机理，可以被视为潜在的治疗靶标。在这项研究中，我们发现骨质疏松症样品中的miR-151a-3p被上调。在MC3T3-E1细胞中进行的实验表明，miR-151a-3p可以显着抑制细胞活力并促进乳酸脱氢酶的释放，并增加RANKL / OPG的比例并降低Runx2和BMP2的表达。SOCS5荧光素酶报告基因检测证实了该蛋白被鉴定为miR-151a-3p的直接靶基因。此外，在骨质疏松症股骨中观察到miR-151a-3p和SOCS5之间呈负相关。此外，发现JAK2 / STAT3途径与miR-151a-3p-SOCS5轴介导的骨质疏松的进展有关。体内建立卵巢切除（OVX）大鼠模型以模拟绝经后骨质疏松症。结果表明，miR-151a-3p通过靶向SOCS5显着降低了OVX大鼠股骨的骨矿物质密度和生物力学参数，而JAK2 / STAT3途径是OVX大鼠miR-151a-3p-SOCS5轴的下游靶标。总之，我们的发现表明miR-151a-3p促成了绝经后骨质疏松的发病机制，并通过靶向SOCS5和激活JAK2 / STAT3信号传导促进了其进展。因此，抗miR-151a-3p可能是绝经后骨质疏松症的潜在治疗策略。