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A regulatory loop containing miR-26a, GSK3β and C/EBPα regulates the osteogenesis of human adipose-derived mesenchymal stem cells
- Source :
- Scientific Reports
- Publication Year :
- 2015
- Publisher :
- Nature Publishing Group, 2015.
-
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 GSK3β, suppressing the expression of GSK3β protein. Similar to the effect of overexpressing miR-26a, the knockdown of GSK3β promoted osteogenic differentiation, whereas GSK3β overexpression inhibited this process, suggesting that GSK3β acted as a negative regulator of hADSC osteogenesis. Furthermore, GSK3β influences Wnt signalling pathway by regulating β-catenin and subsequently altered the expression of its downstream target C/EBPα. In turn, C/EBPα 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, GSK3β and C/EBPα, 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.
- Subjects :
- Beta-catenin
Cellular differentiation
Core Binding Factor Alpha 1 Subunit
Article
Glycogen Synthase Kinase 3
GSK-3
RNA interference
Osteogenesis
microRNA
CCAAT-Enhancer-Binding Protein-alpha
Humans
RNA, Small Interfering
Promoter Regions, Genetic
3' Untranslated Regions
Cells, Cultured
beta Catenin
Gene knockdown
Multidisciplinary
Binding Sites
Glycogen Synthase Kinase 3 beta
biology
Base Sequence
Three prime untranslated region
Mesenchymal stem cell
Cell Differentiation
Mesenchymal Stem Cells
Oligonucleotides, Antisense
Molecular biology
Cell biology
MicroRNAs
Adipose Tissue
Microscopy, Fluorescence
biology.protein
RNA Interference
Sequence Alignment
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....64133761f8c942ab37773e7e86fa1c37
- Full Text :
- https://doi.org/10.1038/srep15280