Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-23
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0736-0266
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
712-9
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
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.
pubmed:affiliation
Department of Orthopaedic Surgery, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, MO 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.