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.