| Literature DB >> 31288577 |
Adil Akkouch1, Steven Eliason2,3, Mason E Sweat2, Miguel Romero-Bustillos4, Min Zhu1, Fang Qian1, Brad A Amendt1,2,3, Liu Hong1,3.
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.Entities:
Keywords: Klf4; Sox2; Wnt; bone; miR-200c; osteogenic
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Year: 2019 PMID： 31288577 PMCID： PMC6854517 DOI： 10.1089/hum.2019.019
Source DB: PubMed Journal: Hum Gene Ther ISSN： 1043-0342 Impact factor: 5.695