Hsa_circ_0122913 suppresses the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells and is involved in the effects of icariin treatment via sponging miR‑501‑5p

Circular RNAs (circRNAs) play significant roles in several biological events. It has been revealed that hsa_circ_0122913 was upregulated in peripheral blood samples from patients with senile osteoporotic vertebral compression fracture. Therefore, the present study aimed to investigate the role of hsa_circ_0122913 in osteoporosis and more particularly its effect on the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In addition, the involvement of hsa_circ_0122913 in the effectiveness of icariin treatment in BMSCs was also explored. For functional experiments, BMSCs were transfected with short hairpin RNAs targeting hsa_circ_0122913 and defective in cullin neddylation 1 domain containing 1 (DCUN1D1). To determine BMSCs viability and apoptosis, Cell Counting Kit 8 (CCK-8) and Annexin V-APC/7-AAD assays were carried out, respectively. Furthermore, the expression levels of hsa_circ_0122913, osteopontin (OPN), runt-related transcription factor 2 (RUNX2), osterix (OSX) and DCUN1D1 were measured by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. The CircBank database was used to predict the potential binding sites of microRNA (miR)-501-5p οn hsa_circ_0122913. The binding capacity of miR-501-5p on hsa_circ_0122913 was then verified by dual-luciferase assay. Finally, alizarin red staining was used to observe the degree of osteogenic differentiation. The CCK-8 and Annexin V-APC/7-AAD assay results demonstrated that hsa_circ_0122913 knockdown in BMSCs improved cell viability and attenuated cell apoptosis. Additionally, the RT-qPCR and western blot analysis results revealed that hsa_circ_0122913 silencing could enhance the mRNA and protein expression levels of OSX, RUNX2 and OPN. Furthermore, the results indicated that hsa_circ_0122913 could sponge miR-501-5p, while the hsa_circ_0122913/DCUN1D1 axis could be involved in the beneficial effects of icariin on BMSCs and more particularly on promoting cell viability and osteogenic differentiation. Overall, the current study suggested that hsa_circ_0122913 could be a novel biomarker for identifying individuals at high risk of osteoporosis, thus being involved in the prevention and treatment of the disease.