Abstract
MicroRNA (miR)-200c functions in antitumorigenesis 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 alkaline phosphatase, Runt-related transcription factor 2, osteocalcin, and mineral deposition. The pDNA encoding miR-200c also significantly enhanced bone formation and regeneration in calvarial defects of rat models. In addition, miR-200c overexpression was shown to downregulate SRY (sex determining region Y)-box 2 (Sox2) and Kruppel-like factor 4 by directly targeting 3'-untranslated regions and upregulate the activity of Wnt signaling inhibited by Sox2. These results strongly indicated that miR-200c may serve as a unique osteoinductive agent applied for bone healing and regeneration.