miR-145-5p suppresses osteogenic differentiation of adipose-derived stem cells by targeting semaphorin 3A.

Adipose-derived stem cells (ADSCs) provide a novel method for bone tissue regeneration, but their adipogenic tendency limits their therapeutic efficacy. MicroRNAs (miRNAs) have been reported to regulate stem cell differentiation and bone tissue regeneration, but the detailed mechanism is poorly investigated. Our study indicated that inhibition of miR-145-5p enhanced the osteogenic potential of ADSCs and reduced the adipogenic differentiation. Osteogenesis- and adipogenesis-associated genes were detected by qRT-PCR indicating a corresponding result. Moreover, semaphorin 3A (sema3A) was found to be a target of miR-145-5p, as confirmed by a luciferase activity assay, qRT-PCR, and western blotting. Inhibition of miR-145-5p promoted migration, as detected by wound healing and Transwell assays, but did not affect proliferation, as detected by CCK-8 and ki-67 assays. The effects of miR-145-5p inhibitors on ADSC progression rescued by siRNA of Sema3a and si-sema3a exerted the same effect as miR-145-5p inhibitors on ADSC progression. Furthermore, siRNA of Sema3a rescued synergistic effects with miR-145-5p inhibitors in ADSCs. qRT-PCR and immunofluorescence assays showed that miR-145-5p activated the Wnt signaling pathway for osteogenic differentiation. In conclusion, miR-145-5p and sema3a represent new targets for improving the osteogenic capacity of ADSCs.