MiR-29a promotes osteogenic differentiation of mesenchymal stem cells via targeting HDAC4.

OBJECTIVE: To investigate the role of miR-29a in regulating the differentiation mesenchymal stem cells into osteoblasts.

MATERIALS AND METHODS: For the first step, the changes of expression of miR-29a during the process of mesenchymal stem cells (MSCs) differentiation into osteoblast were detected. Then, we infected the MSCs with mimics or inhibitors of miR-29a to explore the roles of miR-29a in the differentiation. Further, the prediction and verification of the possible target genes of miR-29a were achieved by bioinformatics analysis and luciferase reporter assay.

RESULTS: MiR-29a was up-regulated during the process of MSCs differentiation into osteoblasts. Overexpression or inhibition of miR-29a using mimics or inhibitors had no significant effect on cell proliferation. Furthermore, the differentiation was enhanced when miR-29a was artificially overexpressed in vitro, whereas silencing of miR-29a attenuated this process. It was evidenced by alkaline phosphatase (ALP) staining, matrix mineralization, and increased expression of osteoblast-specific genes. Furthermore, we determined that the gene HDAC4 might be a direct target of miR-29a.

CONCLUSIONS: In the current study, miR-29a promotes osteogenesis via suppressing HDAC4, indicating that targeting miR-29a may be feasible in the management of osteoporosis.