Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-12-19
pubmed:abstractText
Vascular endothelial growth factor (VEGF) is essential for establishing vascularization and regulating chondrocyte development and survival. We have demonstrated that VEGF regulates the expression of CCN2/connective tissue growth factor (CCN2/CTGF) an essential mediator of cartilage development and angiogenesis, suggesting that CCN2 functions in down-stream of VEGF, and that VEGF function is mediated in part by CCN2. On the other hand, the phenotype of Ccn2 mutant growth plates, which exhibit decreased expression of VEGF in the hypertrophic zone, indicates that Vegf expression is dependent on Ccn2 expression as well. Therefore, we investigated the molecular mechanisms underlying the induction of VEGF by CCN2 using a human chondrocytic cell line, HCS-2/8. Hypoxic stimulation (5% O(2)) of HCS-2/8 cells increased VEGF mRNA levels by approximately 8 fold within 6 h as compared with the cells cultured under normoxia. In addition, VEGF expression was further up-regulated under hypoxia in HCS-2/8 cells transfected with a Ccn2 expression plasmid. Hypoxia-inducible factor (HIF)-1alpha mRNA and protein levels were increased by stimulation with recombinant CCN2 (rCCN2). Furthermore, the activity of a VEGF promoter that contained a HIF-1 binding site was increased in HCS-2/8, when the cells were stimulated by rCCN2. These results suggest that CCN2 regulates the expression of VEGF at a transcriptional level by promoting HIF-1alpha activity. In fact, HIF-1alpha was detected in the nuclei of proliferative and pre-hypertrophic chondrocytes of wild-type mice, whereas it was not detected in Ccn2 mutant chondrocytes in vivo. This activation cascade from CCN2 to VEGF may therefore play a critical role in chondrocyte development and survival.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-10393331, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-10614647, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-10867644, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-11479208, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-11486006, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-11691837, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-11721179, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-11744618, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12016149, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12114504, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12115736, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12134160, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12548546, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12682668, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12736220, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12748653, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-12811819, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-14722611, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-14723997, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-15006615, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-15073147, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-15135139, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-15231019, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-15526358, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-16247469, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-16432171, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-16849681, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-16887934, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-17034590, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-17280894, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-17625227, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-17875658, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-17908800, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-18481209, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-2071232, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-2736538, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-8200849, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-8756616, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-9168990, http://linkedlifedata.com/resource/pubmed/commentcorrection/18835464-9647791
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-2763
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
24-31
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
CCN family 2/connective tissue growth factor (CCN2/CTGF) regulates the expression of Vegf through Hif-1alpha expression in a chondrocytic cell line, HCS-2/8, under hypoxic condition.
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