CircSmg5 stimulates the osteogenic differentiation of bone marrow mesenchymal stem cells by targeting the miR-194-5p/Fzd6 axis and beta-catenin signaling.

Abstract

Osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is closely associated with bone diseases. Circular RNAs are reported to be involved in BMSC differentiation. CircSmg5 (circ_0001145) has been identified to be downregulated in an osteoporosis mouse model. In this study, we aimed to explore the function and regulatory mechanism of circSmg5 in BMSC osteogenic differentiation. The Alizarin Red staining and alkaline phosphatase staining assays were performed to explore the osteogenic differentiation of BMSCs. The interaction between circ_0001145, miR-194-5p, and frizzled class receptor 6 (Fzd6) was analyzed by luciferase reporter assay. The nuclear translocation of β-catenin was assessed using immunofluorescence staining. CircSmg5 is in stable circular structure. CircSmg5 expression was elevated in the process of BMSC osteogenic differentiation. CircSmg5 overexpression promoted the osteogenic differentiation of BMSCs. CircSmg5 bound with miR-194-5p, whose expression was decreased in the osteogenic differentiation of BMSCs. MiR-194-5p directly targeted the 3'UTR of Fzd6. The mRNA and protein levels of Fzd6 were positively modulated by circSmg5 and negatively regulated by miR-194-5p in BMSCs. CircSmg5 was demonstrated to promote the BMSC osteogenic differentiation by targeting the miR-194-5p/Fzd6 axis to activate the Wnt/β-catenin signaling.