The authors state that they have no conflicts of interest.
miR-196a Regulates Proliferation and Osteogenic Differentiation in Mesenchymal Stem Cells Derived From Human Adipose Tissue†
Article first published online: 8 DEC 2008
Copyright © 2009 ASBMR
Journal of Bone and Mineral Research
Volume 24, Issue 5, pages 816–825, May 2009
How to Cite
Kim, Y. J., Bae, S. W., Yu, S. S., Bae, Y. C. and Jung, J. S. (2009), miR-196a Regulates Proliferation and Osteogenic Differentiation in Mesenchymal Stem Cells Derived From Human Adipose Tissue. J Bone Miner Res, 24: 816–825. doi: 10.1359/jbmr.081230
- Issue published online: 4 DEC 2009
- Article first published online: 8 DEC 2008
- Manuscript Accepted: 5 DEC 2008
- Manuscript Revised: 29 SEP 2008
- Manuscript Received: 15 JUL 2008
- human adipose tissue-derived mesenchymal stem cells;
- osteogenic differentiation;
The elucidation of the molecular mechanisms that govern the differentiation and proliferation of human adipose tissue-derived mesenchymal stem cells (hASCs) could improve hASC-based cell therapy. In this study, we examined the roles of microRNA (miRNA)-196a on hASC proliferation and osteogenic differentiation. Lentiviral overexpression of miR-196a decreased hASC proliferation and enhanced osteogenic differentiation, without affecting adipogenic differentiation. Overexpression of miR-196a decreased the protein and mRNA levels of HOXC8, a predicted target of miR-196a. HOXC8 expression was decreased during osteogenic differentiation of hASCs, and this decrease in HOXC8 expression was concomitant with an increase in the level of miR-196a. In contrast, inhibition of miR-196a with 2′-O-methyl-antisense RNA increased the protein levels of HOXC8 in treated hASCs and was accompanied by increased proliferation and decreased osteogenic differentiation. The activity of a luciferase construct containing the miR-196a target site from the HOXC8 3′UTR was lower in LV-miR196a-infected hASCs than in LV-miLacZ-infected cells. RNA interference-mediated downregulation of HOXC8 in hASCs increased their proliferation and decreased their differentiation into osteogenic cells, without affecting their adipogenic differentiation. Our data indicate that miR-196a plays a role in hASC osteogenic differentiation and proliferation, which may be mediated through its predicted target, HOXC8. This study provides us with a better knowledge of the molecular mechanisms that govern hASC differentiation and proliferation.