FOXO3A Regulation by miRNA-29a Controls Chondrogenic Differentiation of Mesenchymal Stem Cells and Cartilage Formation
| Autor: | Didier Philipot, Jean-Marc Brondello, Christian Jorgensen, Claire Bony, Karine Toupet, Paul Chuchana, David Guérit, Danièle Noël |
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| Přispěvatelé: | Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) |
| Rok vydání: | 2014 |
| Předmět: |
[SDV]Life Sciences [q-bio]
SOX9 Biology Mice 03 medical and health sciences Chondrocytes 0302 clinical medicine Osteogenesis Transcription (biology) microRNA Animals Humans Cells Cultured 030304 developmental biology Regulation of gene expression 0303 health sciences Forkhead Box Protein O3 Mesenchymal stem cell Cell Differentiation Forkhead Transcription Factors Mesenchymal Stem Cells Cell Biology Hematology Transfection Chondrogenesis Molecular biology Cell biology MicroRNAs Cartilage Gene Expression Regulation 030220 oncology & carcinogenesis Chromatin immunoprecipitation Developmental Biology |
| Zdroj: | Stem Cells and Development Stem Cells and Development, Mary Ann Liebert, 2014, 23 (11), pp.1195-1205. ⟨10.1089/scd.2013.0463⟩ |
| ISSN: | 1557-8534 1547-3287 |
| Popis: | International audience; Skeletal development and cartilage formation require stringent regulation of gene expression for mesenchymal stem cells (MSCs) to progress through stages of differentiation. Since microRNAs (miRNAs) regulate biological processes, the objective of the present study was to identify novel miRNAs involved in the modulation of chondrogenesis. We performed miRNA profiling and identify miR-29a as being one of the most down-regulated miRNAs during the chondrogenesis. Using chromatin immunoprecipitation, we showed that SOX9 down-regulates its transcription. Moreover, the over-expression of miR-29a strongly inhibited the expression of chondrocyte-specific markers during in vitro chondrogenic differentiation of MSCs. We identified FOXO3A as a direct target of miR-29a and showed a down- and up-regulation of FOXO3a protein levels after transfection of, respectively, premiR- and antagomiR-29a oligonucleotides. Finally, we showed that using the siRNA or premiR approach, chondrogenic differentiation was inhibited to a similar extent. Together, we demonstrate that the down-regulation of miR-29a, concomitantly with FOXO3A up-regulation, is essential for the differentiation of MSCs into chondrocytes and in vivo cartilage/bone formation. The delivery of miRNAs that modulate MSC chondrogenesis may be applicable for cartilage regeneration and deserves further investigation. |
| Databáze: | OpenAIRE |
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