Background: 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.
Methods: 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.
Results: 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.
Conclusion: CircSmg5 was demonstrated to promote the BMSC osteogenic differentiation by targeting the miR-194-5p/Fzd6 axis to activate the Wnt/β-catenin signaling.
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