MicroRNA-135a-5p is Involved in Osteoporosis Progression Through Regulation of Osteogenic Differentiation by Targeting RUNX2

A number of microRNAs (miRs) have been revealed to be involved in the development of osteoporosis, including postmenopausal osteoporosis. The aim of the present study was to investigate miR-135a-5p expression and the cellular function of miR-135a-5p and its underlying mechanism in postmenopausal osteoporosis. miR-135a-5p expression levels in the femoral neck trabecular bone tissue fragments from postmenopausal women with or without osteoporosis were detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The role of miR-135a-5p during osteogenic differentiation was examined by performing gain- and loss-of-function experiments using miR-135a-5p mimic or inhibitor. TargetScan bioinformatics analysis was sued to predict targets of miR-135a-5p, which were confirmed using luciferase reporter assays. miR-135a-5p expression was significantly upregulated in femoral neck trabecular bone tissue fragments from postmenopausal women with osteoporosis compared with postmenopausal women without osteoporosis. In addition, miR-135a-5p expression levels significantly decreased during osteogenic differentiation in the C2C12 cell model. miR-135a-5p overexpression decreased the osteogenic potential of C2C12 cells, as miR-135a-5p overexpression significantly reduced the expression levels of several key osteoblast markers, whilst miR-135a-5p knockdown had the opposite effect. Furthermore, the current study demonstrated that RUNX2 was a direct target of miR-135a-5p. Rescue experiments indicated that RUNX2 overexpression significantly reversed the effect of miR-135a-5p mimic on the osteogenic potential of C2C12 cells, indicating that miR-135a-5p mediates osteogenic differentiation via direct targeting of RUNX2. Taken together, these results suggest that miR-135a-5p may serve a role in osteoporosis progression by regulating osteogenic differentiation via RUNX2.