Sox9-Regulated miRNA-574-3p Inhibits Chondrogenic Differentiation of Mesenchymal Stem Cells
Open Access
- 23 April 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (4), e62582
- https://doi.org/10.1371/journal.pone.0062582
Abstract
The aim of this study was to identify new microRNAs (miRNAs) that are modulated during the differentiation of mesenchymal stem cells (MSCs) toward chondrocytes. Using large scale miRNA arrays, we compared the expression of miRNAs in MSCs (day 0) and at early time points (day 0.5 and 3) after chondrogenesis induction. Transfection of premiRNA or antagomiRNA was performed on MSCs before chondrogenesis induction and expression of miRNAs and chondrocyte markers was evaluated at different time points during differentiation by RT-qPCR. Among miRNAs that were modulated during chondrogenesis, we identified miR-574-3p as an early up-regulated miRNA. We found that miR-574-3p up-regulation is mediated via direct binding of Sox9 to its promoter region and demonstrated by reporter assay that retinoid X receptor (RXR)α is one gene specifically targeted by the miRNA. In vitro transfection of MSCs with premiR-574-3p resulted in the inhibition of chondrogenesis demonstrating its role during the commitment of MSCs towards chondrocytes. In vivo , however, both up- and down-regulation of miR-574-3p expression inhibited differentiation toward cartilage and bone in a model of heterotopic ossification. In conclusion, we demonstrated that Sox9-dependent up-regulation of miR-574-3p results in RXRα down-regulation. Manipulating miR-574-3p levels both in vitro and in vivo inhibited chondrogenesis suggesting that miR-574-3p might be required for chondrocyte lineage maintenance but also that of MSC multipotency.This publication has 34 references indexed in Scilit:
- A Catalogue of Glioblastoma and Brain MicroRNAs Identified by Deep SequencingOMICS: A Journal of Integrative Biology, 2012
- Aberrant expression of microRNAs in gastric cancer and biological significance of miR-574-3pInternational Immunopharmacology, 2012
- A miR-1231 binding site polymorphism in the 3′UTR of IFNAR1 is associated with hepatocellular carcinoma susceptibilityGene, 2012
- MicroRNA-337 is associated with chondrogenesis through regulating TGFBR2 expressionOsteoarthritis and Cartilage, 2012
- MiR-194 Regulates Chondrogenic Differentiation of Human Adipose-Derived Stem Cells by Targeting Sox5PLOS ONE, 2012
- Epigenomic and microRNA-mediated regulation in cartilage development, homeostasis, and osteoarthritisTrends in Molecular Medicine, 2012
- The expression and function of microRNAs in chondrogenesis and osteoarthritisArthritis & Rheumatism, 2011
- Requirement for RAR-mediated gene repression in skeletal progenitor differentiationThe Journal of cell biology, 2002
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- Differential expression of the retinoic acid-metabolizing enzymes CYP26A1 and CYP26B1 during murine organogenesisMechanisms of Development, 2001