PloS one, 2011-07, Vol.6 (7), p.e21679
2011
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- Autor(en) / Beteiligte
- Titel
- MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9
- Ist Teil von
- PloS one, 2011-07, Vol.6 (7), p.e21679
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3'-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0021679Titel-ID: cdi_plos_journals_1306360200
- Format
- –
- Schlagworte
- 3' Untranslated regions, 3' Untranslated Regions - genetics, Aggrecan, Animals, Apoptosis, Base Sequence, Binding sites, Biological activity, Biology, Biomechanics, Bone marrow, Bone morphogenetic proteins, Cartilage, Cartilage oligomeric matrix protein, Cascades, Cell Differentiation - drug effects, Cell Differentiation - genetics, Cell Line, Chondrogenesis, Chondrogenesis - drug effects, Chondrogenesis - genetics, Collagen (type II), Collagen (type IX), Differentiation, DNA binding proteins, Down-Regulation - drug effects, Down-Regulation - genetics, Gene expression, Genes, Genes, Reporter - genetics, Genotype & phenotype, Growth factors, High mobility group proteins, Homeostasis, Kinases, Laboratories, Luciferase, Luciferases - genetics, Matrix protein, Mesenchymal stem cells, Mesenchymal Stem Cells - cytology, Mesenchymal Stem Cells - drug effects, Mesenchymal Stem Cells - metabolism, Mesenchyme, Mice, MicroRNA, MicroRNAs, MicroRNAs - genetics, MicroRNAs - metabolism, miRNA, Overexpression, Protein binding, Protein biosynthesis, Protein expression, Protein synthesis, Proteins, Reporter gene, Ribonucleic acid, RNA, Signaling, Smooth muscle, Sox9 protein, SOX9 Transcription Factor - genetics, SOX9 Transcription Factor - metabolism, Stem cell transplantation, Stem cells, Studies, Transcription (Genetics), Transcription factors, Transforming Growth Factor beta3 - pharmacology, Transforming growth factor-b1, Transforming growth factors