MicroRNA-200c Promotes Bone Regeneration By Targeting SOX2-Mediated WNT Signaling And KLF4
MicroRNA (miR)-200c functions in anti-tumorigenesis and mediates inflammation and osteogenic differentiation. In this study, we discovered that miR-200c was upregulated in human bone marrow mesenchymal stromal cells (hBMSCs) during osteogenic differentiation. Inhibition of endogenous miR-200c resulted in downregulated osteogenic differentiation of hBMSCs and reduced bone volume in the maxilla and mandible of a transgenic mouse model. Overexpression of miR-200c by transfection of naked plasmid DNA (pDNA) encoding miR-200c significantly promoted the biomarkers of osteogenic differentiation in hBMSCs, including ALP, RUNX-2, OCN, and mineral deposition. The pDNA encoding miR-200c also significantly enhanced bone formation and regeneration in calvarial defects of rat models. Additionally, miR-200c overexpression was shown to downregulate Sox2 and KLF4 by directly targeting 3'UTRs and upregulate the activity of Wnt signaling inhibited by Sox2. These results strongly indicated that miR-200c may serve as a unique osteo-inductive agent applied for bone healing and regeneration.