Open AccessEnhancement of MicroRNA-200c on Osteogenic Differentiation and Bone Regeneration by Targeting Sox2-Mediated Wnt Signaling and Klf4
Author(s) -
Adil Akkouch,
Steven Eliason,
Mason Sweat,
Miguel RomeroBustillos,
Mingqing Zhu,
Fang Qian,
Brad A. Amendt,
Liu Hong
Publication year - 2019
Publication title -
human gene therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.633
H-Index - 149
eISSN - 1557-7422
pISSN - 1043-0342
DOI - 10.1089/hum.2019.019
Subject(s) - sox2 , wnt signaling pathway , microbiology and biotechnology , osteocalcin , downregulation and upregulation , stromal cell , chemistry , mesenchymal stem cell , regeneration (biology) , cellular differentiation , klf4 , alkaline phosphatase , transcription factor , biology , cancer research , signal transduction , biochemistry , gene , enzyme
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.