MiR-151a-3p Promotes Postmenopausal Osteoporosis by Targeting SOCS5 and Activating JAK2/STAT3 Signaling

作者：Yin Fu, Yier Xu, Shuilin Chen, Yulong Ouyang, Guicai Sun · 发表于：Rejuvenation Research · 年份：2019 · DOI：10.1089/rej.2019.2239 · 被引用次数：68 · 研究领域：MicroRNA in disease regulation、Bone Metabolism and Diseases、Cytokine Signaling Pathways and Interactions

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, a...