A regulatory loop containing miR-26a, GSK3? and C/EBP? regulates the osteogenesis of human adipose-derived mesenchymal stem cells.

ABSTRACT: Elucidating the molecular mechanisms responsible for osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) will provide deeper insights into the regulatory mechanisms of this process and help develop more efficient methods for cell-based therapies. In this study, we analysed the role of miR-26a in the regulation of hADSC osteogenesis. The endogenous expression of miR-26a increased during the osteogenic differentiation. The overexpression of miR-26a promoted hADSC osteogenesis, whereas osteogenesis was repressed by miR-26a knockdown. Additionally, miR-26a directly targeted the 3'UTR of the GSK3?, suppressing the expression of GSK3? protein. Similar to the effect of overexpressing miR-26a, the knockdown of GSK3? promoted osteogenic differentiation, whereas GSK3? overexpression inhibited this process, suggesting that GSK3? acted as a negative regulator of hADSC osteogenesis. Furthermore, GSK3? influences Wnt signalling pathway by regulating ?-catenin, and subsequently altered the expression of its downstream target C/EBP?. In turn, C/EBP? transcriptionally regulated the expression of miR-26a by physically binding to the CTDSPL promoter region. Taken together, our data identified a novel feedback regulatory circuitry composed of miR-26a, GSK3? and C/EBP?, the function of which might contribute to the regulation of hADSC osteogenesis. Our findings provided new insights into the function of miR-26a and the mechanisms underlying osteogenesis of hADSCs.

SUBMITTER: Wang Z 

PROVIDER: S-EPMC4606799 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature