It is known that miRNA mediates the formation of osteogenesis, but the mechanism by which miRNA let-7a-5p regulates osteogenesis in osteoporosis (OP) is not yet understood. This paper aims to probe into the regulatory mechanism of miRNA let-7a-5p in the development of OP. Fresh femoral trabecular bones of patients with osteoporotic fracture (OP group, n = 25) and non-OP osteoarthritis (Non-OP group, n = 23) who underwent hip replacement in our hospital from December 2016 to December 2019 were collected. The expression and protein levels of miRNA let-7a-5p and V-AKT murine thymoma viral oncogene homolog 3 (RNA KCNQ1OT1) were detected. C2C12 cells were purchased and osteogenic differentiation model was constructed by BMP2 induction. After miRNA let-7a-5p up-regulation or down-regulation by transfection of corresponding mimics and inhibitors, the impacts of miRNA let-7a-5p and RNA KCNQ1OT1 on osteogenic differentiation-related factors (OC, ALP, COL1A1) in C2C12 cells were analyzed. The determination of targeting correlation of miRNA let-7a-5p with RNA KCNQ1OT1 was performed by dual-luciferase reporter (DLR). In OP samples, miRNA let-7a-5p was notably declined while RNA KCNQ1OT1 were remarkably up-regulated. MiRNA let-7a-5p reduced in C2C12 cells as BMP2 treatment proceeded. MiRNA let-7a-5p up-regulation or RNA KCNQ1OT1 down-regulation increased OC, ALP, COL1A1 levels and ALP activity. RNA KCNQ1OT1 was directly targeted to miR-497-5p. RNA KCNQ1OT1 up-regulation weakened the promoting effect of miRNA let-7a-5p up-regulation on osteoblast differentiation. MiRNA let-7a-5p up-regulation can target to reduce RNA KCNQ1OT1 and promote osteoblast differentiation, thereby improving the development of osteoporosis.

已知miRNA介导成骨形成，但miRNA let-7a-5p在骨质疏松症(OP)中调节成骨的机制尚不清楚。本文旨在探讨miRNA let-7a-5p在OP发生发展中的调控机制。骨质疏松性骨折（OP 组，n  = 25）和非 OP 骨关节炎（Non-OP 组，n = 23) 收集 2016 年 12 月至 2019 年 12 月在我院接受髋关节置换术的患者。检测miRNA let-7a-5p和V-AKT鼠胸腺瘤病毒癌基因同源物3（RNA KCNQ1OT1）的表达和蛋白水平。购买C2C12细胞，通过BMP2诱导构建成骨分化模型。miRNA let-7a-5p通过转染相应模拟物和抑制剂上调或下调后，miRNA let-7a-5p和RNA KCNQ1OT1对C2C12细胞成骨分化相关因子（OC、ALP、COL1A1）的影响进行了分析。通过双荧光素酶报告基因 (DLR) 确定 miRNA let-7a-5p 与 RNA KCNQ1OT1 的靶向相关性。在 OP 样本中，miRNA let-7a-5p 显着下降，而 RNA KCNQ1OT1 显着上调。随着 BMP2 处理的进行，C2C12 细胞中的 miRNA let-7a-5p 减少。MiRNA let-7a-5p 上调或 RNA KCNQ1OT1 下调增加了 OC、ALP、COL1A1 水平和 ALP 活性。RNA KCNQ1OT1 直接靶向 miR-497-5p。RNA KCNQ1OT1上调减弱了miRNA let-7a-5p上调对成骨细胞分化的促进作用。miRNA let-7a-5p 上调可以靶向减少 RNA KCNQ1OT1 并促进成骨细胞分化，从而改善骨质疏松症的发展。