Source:http://linkedlifedata.com/resource/pubmed/id/11518283
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2001-8-23
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pubmed:abstractText |
Cartilage-derived retinoic acid-sensitive protein (CD-RAP) is a secreted protein identified in our laboratory by RT-PCR and differential display [U.H. Dietz, L.J. Sandell. Cloning of a retinoic acid-sensitive mDNA expressed in cartilage and during chondrogenesis. J. Biol. Chem. 271 (1996) 3311-3316]. It is synthesized by chondrocytes throughout development and down-regulated by retinoic acid in coordination with type II collagen gene expression. To further explore the regulation CD-RAP in primary articular chondrocytes, we examined effects of selected cytokines on CD-RAP gene expression compared to their effects on type II collagen expression. Northern blot analysis showed that expression of CD-RAP mRNA was suppressed by bFGF, IL-1beta and retinoic acid in coordination with type II collagen mRNA. TGF-beta decreased CD-RAP expression while increasing type II collagen mRNA whereas both mRNAs were up-regulated by IGF-1. In chondrocytes dedifferentiated with retinoic acid, IGF-1 induced re-expression of both CD-RAP and type II collagen mRNAs. The mechanism of stimulation of CD-RAP by IGF-1 was further investigated. An mRNA stability assay revealed that IGF-1 had no effect on CD-RAP or type II collagen mRNA half life, suggesting that the enhancement by IGF-1 is due to increased gene transcription. To study the transcriptional mechanism, we used the 5'-flanking region of the CD-RAP gene fused to a promoter-less reporter plasmid encoding luciferase. Deletion analysis of the CD-RAP promoter indicated that an IGF-1-responsive element is present between nucleotides -475 and -458. These data indicate that CD-RAP expression can be regulated by cytokines known to influence chondrocyte metabolism and that IGF-1 up-regulates CD-RAP gene expression through a transcriptional mechanism.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Collagen,
http://linkedlifedata.com/resource/pubmed/chemical/Fibroblast Growth Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0736-0266
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
712-9
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11518283-Animals,
pubmed-meshheading:11518283-Cartilage, Articular,
pubmed-meshheading:11518283-Cattle,
pubmed-meshheading:11518283-Cells, Cultured,
pubmed-meshheading:11518283-Chondrocytes,
pubmed-meshheading:11518283-Collagen,
pubmed-meshheading:11518283-Fibroblast Growth Factor 2,
pubmed-meshheading:11518283-Gene Deletion,
pubmed-meshheading:11518283-Gene Expression Regulation,
pubmed-meshheading:11518283-Insulin-Like Growth Factor I,
pubmed-meshheading:11518283-Interleukin-1,
pubmed-meshheading:11518283-Phenotype,
pubmed-meshheading:11518283-Promoter Regions, Genetic,
pubmed-meshheading:11518283-Proteins,
pubmed-meshheading:11518283-RNA, Messenger,
pubmed-meshheading:11518283-Transforming Growth Factor beta
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pubmed:year |
2001
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pubmed:articleTitle |
Cytokine regulation of cartilage-derived retinoic acid-sensitive protein (CD-RAP) in primary articular chondrocytes: suppression by IL-1, bfGF, TGFbeta and stimulation by IGF-1.
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pubmed:affiliation |
Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.
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