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rdf:type |
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lifeskim:mentions |
umls-concept:C0040648,
umls-concept:C0086860,
umls-concept:C0179400,
umls-concept:C0205107,
umls-concept:C0262950,
umls-concept:C0279266,
umls-concept:C0598067,
umls-concept:C1420331,
umls-concept:C1554080,
umls-concept:C1704259,
umls-concept:C1705987,
umls-concept:C1706198,
umls-concept:C1879547
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pubmed:issue |
1
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pubmed:dateCreated |
2008-7-29
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pubmed:abstractText |
Mouse embryonic fibroblasts (MEFs) can be differentiated into fully functional chondrocytes in response to bone morphogenetic protein-2 (BMP-2). The expression of Sox9, a critical transcription factor for the multiple steps of chondrogenesis, has been reported to be upregulated during this process. But the molecular mechanisms by which BMP-2 promotes chondrogenesis still remain largely unknown. The aim of the present study was therefore to investigate the underlying mechanism. In the MEFs, BMP-2 efficiently induced Sox9 expression along with chondrogenic differentiation in a time- and dose-dependent manner. SB203580, a specific inhibitor for p38 pathway, blocked BMP-2-induced chondrogenic differentiation as well as Sox9 expression and its transactivation of downstream genes. Forced expression of Smad6, a natural antagonist for BMP/Smad pathway, only inhibited Sox9 protein function without rendering any effects on its mRNA expression. A CCAAT box was identified in Sox9 promoter as the cis-elements responsible for BMP-2 stimulation. This study provides insight into the mechanisms underlying BMP-2-regulated Sox9 expression and activity in MEFs, and suggests differential roles of BMP-2/p38 and BMP-2/Smad pathways in modulating the function of Sox9 during chondrogenesis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BMP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/High Mobility Group Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SOX9 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/SOX9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad6 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad6 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Sox9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1097-4652
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2008 Wiley-Liss, Inc.
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pubmed:issnType |
Electronic
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pubmed:volume |
217
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
228-41
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18506848-Animals,
pubmed-meshheading:18506848-Base Sequence,
pubmed-meshheading:18506848-Blotting, Western,
pubmed-meshheading:18506848-Bone Morphogenetic Protein 2,
pubmed-meshheading:18506848-Bone Morphogenetic Proteins,
pubmed-meshheading:18506848-Cell Differentiation,
pubmed-meshheading:18506848-Cells, Cultured,
pubmed-meshheading:18506848-Chickens,
pubmed-meshheading:18506848-Chondrogenesis,
pubmed-meshheading:18506848-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18506848-Enzyme Activation,
pubmed-meshheading:18506848-Enzyme Inhibitors,
pubmed-meshheading:18506848-Fibroblasts,
pubmed-meshheading:18506848-Gene Expression Regulation,
pubmed-meshheading:18506848-High Mobility Group Proteins,
pubmed-meshheading:18506848-Humans,
pubmed-meshheading:18506848-Mice,
pubmed-meshheading:18506848-Mice, Inbred BALB C,
pubmed-meshheading:18506848-Molecular Sequence Data,
pubmed-meshheading:18506848-Promoter Regions, Genetic,
pubmed-meshheading:18506848-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18506848-SOX9 Transcription Factor,
pubmed-meshheading:18506848-Sequence Homology, Nucleic Acid,
pubmed-meshheading:18506848-Smad6 Protein,
pubmed-meshheading:18506848-Transcription Factors,
pubmed-meshheading:18506848-Transfection,
pubmed-meshheading:18506848-Transforming Growth Factor beta,
pubmed-meshheading:18506848-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2008
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pubmed:articleTitle |
Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter.
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pubmed:affiliation |
Medical Research Center, the Second Affiliated Hospital, Sun Yat-sen University, Guangzhou City, Guangdong Province, PR China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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