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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
43
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pubmed:dateCreated |
2009-10-19
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pubmed:abstractText |
Transforming growth factor beta (TGFbeta) signaling has an increasing interest in regenerative medicine as a potential tool to repair cartilages, however the chondrogenic effect of this pathway in developing systems is controversial. Here we have analyzed the function of TGFbeta signaling in the differentiation of the developing limb mesoderm in vivo and in high density micromass cultures. In these systems highest signaling activity corresponded with cells at stages preceding overt chondrocyte differentiation. Interestingly treatments with TGFbetas shifted the differentiation outcome of the cultures from chondrogenesis to fibrogenesis. This phenotypic reprogramming involved down-regulation of Sox9 and Aggrecan and up-regulation of Scleraxis, and Tenomodulin through the Smad pathway. We further show that TGFbeta signaling up-regulates Sox9 in the in vivo experimental model system in which TGFbeta treatments induce ectopic chondrogenesis. Looking for clues explaining the dual role of TGFbeta signaling, we found that TGFbetas appear to be direct inducers of the chondrogenic gene Sox9, but the existence of transcriptional repressors of TGFbeta signaling modulates this role. We identified TGF-interacting factor Tgif1 and SKI-like oncogene SnoN as potential candidates for this inhibitory function. Tgif1 gene regulation by TGFbeta signaling correlated with the differential chondrogenic and fibrogenic effects of this pathway, and its expression pattern in the limb marks the developing tendons. In functional experiments we found that Tgif1 reproduces the profibrogenic effect of TGFbeta treatments.
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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/Aggrecans,
http://linkedlifedata.com/resource/pubmed/chemical/Avian Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SCX protein, Gallus gallus,
http://linkedlifedata.com/resource/pubmed/chemical/SOX9 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Scx protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Skil protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sox9 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tgif protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tnmd protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
23
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pubmed:volume |
284
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
29988-96
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pubmed:dateRevised |
2010-10-26
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pubmed:meshHeading |
pubmed-meshheading:19717568-Aggrecans,
pubmed-meshheading:19717568-Animals,
pubmed-meshheading:19717568-Avian Proteins,
pubmed-meshheading:19717568-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:19717568-Cartilage,
pubmed-meshheading:19717568-Cell Differentiation,
pubmed-meshheading:19717568-Chick Embryo,
pubmed-meshheading:19717568-Chondrocytes,
pubmed-meshheading:19717568-Gene Expression Regulation, Developmental,
pubmed-meshheading:19717568-Hindlimb,
pubmed-meshheading:19717568-Homeodomain Proteins,
pubmed-meshheading:19717568-Membrane Proteins,
pubmed-meshheading:19717568-Mesoderm,
pubmed-meshheading:19717568-Mice,
pubmed-meshheading:19717568-Proto-Oncogene Proteins,
pubmed-meshheading:19717568-Repressor Proteins,
pubmed-meshheading:19717568-SOX9 Transcription Factor,
pubmed-meshheading:19717568-Signal Transduction,
pubmed-meshheading:19717568-Tendons,
pubmed-meshheading:19717568-Transforming Growth Factor beta
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pubmed:year |
2009
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pubmed:articleTitle |
Transforming growth factors beta coordinate cartilage and tendon differentiation in the developing limb mesenchyme.
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pubmed:affiliation |
Departamento de Anatomía y Biología Celular, Universidad de Cantabria, Santander 39011, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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