CircRNA hsa_circ_0006215 promotes osteogenic differentiation of BMSCs and enhances osteogenesis-angiogenesis coupling by competitively binding to miR-942-5p and regulating RUNX2 and VEGF

Coupling between osteogenesis and angiogenesis determines bone morphology. A decrease in the osteogenic ability of bone marrow mesenchymal stem cells (BMSCs) is one of the underlying causes of senile osteoporosis (OP). Here, we investigated the involvement of circular RNAs (circRNAs) in the osteogenic differentiation of BMSCs and the pathogenesis of senile OP. We sequenced RNA and found decreases expression of hsa_circ_0006215 in BMSCs from patients with OP. We further assessed the role of hsa_circ_0006215 in the osteogenic differentiation of BMSCs using lentivirus-mediated hsa_circ_0006215 overexpression and knockdown. Overexpression of hsa_circ_0006215 promoted the osteogenic differentiation of BMSCs. Luciferase reporter and RNA pull-down assays revealed that hsa_circ_0006215 bound to miRNA-942-5p and thus regulated RUNX2 and vascular endothelial growth factor (VEGF) expression in BMSCs. We assessed osteogenesis and vascular coupling in co-cultured cells, and the role of hsa_circ_0006215 in bone formation in vivo using a cortical bone defect model. We found that hsa_circ_0006215 promoted bone defect repair. Overall, our results showed that hsa_circ_0006215 has an important function in osteogenesis and could be a novel target for treating senile OP.