Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells.
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 chondro...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3633883?pdf=render |
| _version_ | 1818059495956283392 |
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| author | David Guérit Didier Philipot Paul Chuchana Karine Toupet Jean-Marc Brondello Marc Mathieu Christian Jorgensen Danièle Noël |
| author_facet | David Guérit Didier Philipot Paul Chuchana Karine Toupet Jean-Marc Brondello Marc Mathieu Christian Jorgensen Danièle Noël |
| author_sort | David Guérit |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T13:17:26Z |
| format | Article |
| id | doaj.art-631868b9e62d40149e93799603666b41 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T13:17:26Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-631868b9e62d40149e93799603666b412022-12-22T01:47:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0184e6258210.1371/journal.pone.0062582Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells.David GuéritDidier PhilipotPaul ChuchanaKarine ToupetJean-Marc BrondelloMarc MathieuChristian JorgensenDanièle NoëlThe 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.http://europepmc.org/articles/PMC3633883?pdf=render |
| spellingShingle | David Guérit Didier Philipot Paul Chuchana Karine Toupet Jean-Marc Brondello Marc Mathieu Christian Jorgensen Danièle Noël Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. PLoS ONE |
| title | Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. |
| title_full | Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. |
| title_fullStr | Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. |
| title_full_unstemmed | Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. |
| title_short | Sox9-regulated miRNA-574-3p inhibits chondrogenic differentiation of mesenchymal stem cells. |
| title_sort | sox9 regulated mirna 574 3p inhibits chondrogenic differentiation of mesenchymal stem cells |
| url | http://europepmc.org/articles/PMC3633883?pdf=render |
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