Linked Life Data

11682465

Source:http://linkedlifedata.com/resource/pubmed/id/11682465

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-1-7
pubmed:abstractText
Synovial fluid basic calcium phosphate (BCP) crystals are common in osteoarthritis and are associated with severe degenerative arthropathy. Besides stimulating synovial fibroblast-like cells to proliferate, BCP crystals are a potent inducer of human matrix metalloproteinases (hMMPs), which can speed up the articular joint tissue degeneration of osteoarthritis patients. Here, we report that transfections with hMMP1 luciferase reporter plasmids in fibroblast-like synoviocytes revealed that the induction of hMMP1 promoter by BCP crystals was mainly mediated through the -72AP-1 element. Elimination of the -72AP-1 element either by mutation or deletion abolished the induction of hMMP1 promoter activity by BCP crystals almost completely. Interestingly, a mutation at the -88PEA-3 site also abolished the induction of hMMP1 promoter. Further mutation at the -181AP-1 site resumed the induction, indicating that the -181AP-1 element had an effect opposite to the -72AP-1 element. The effect of -181AP-1 could be inactivated either by a mutation at this -181AP-1 site or by the -88PEA-3 element. In addition, dominant negative Ras, Raf, and MEK1/2 could block the induction of hMMP1, and a MEK1/2-specific inhibitor (UO126) could block the induction of hMMP1 and c-Fos by BCP crystals. Taken together, these data indicate that multiple elements, including at least AP-1 and PEA-3, are involved in the induction of hMMP1 gene expression by BCP crystals and that the induction follows the Ras/MAPK/c-Fos/AP-1/MMP1 signaling pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1544-52
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11682465-Animals, pubmed-meshheading:11682465-Calcium Phosphates, pubmed-meshheading:11682465-Cells, Cultured, pubmed-meshheading:11682465-Dogs, pubmed-meshheading:11682465-Gene Expression Regulation, Enzymologic, pubmed-meshheading:11682465-Genes, Reporter, pubmed-meshheading:11682465-Humans, pubmed-meshheading:11682465-Matrix Metalloproteinase 1, pubmed-meshheading:11682465-Mitogen-Activated Protein Kinases, pubmed-meshheading:11682465-Mutagenesis, Site-Directed, pubmed-meshheading:11682465-Osteoarthritis, pubmed-meshheading:11682465-Promoter Regions, Genetic, pubmed-meshheading:11682465-Proto-Oncogene Proteins c-fos, pubmed-meshheading:11682465-Recombinant Fusion Proteins, pubmed-meshheading:11682465-Signal Transduction, pubmed-meshheading:11682465-Synovial Membrane, pubmed-meshheading:11682465-Transcription Factors, pubmed-meshheading:11682465-ras GTPase-Activating Proteins
pubmed:year
2002
pubmed:articleTitle
Basic calcium phosphate crystals induce matrix metalloproteinase-1 through the Ras/mitogen-activated protein kinase/c-Fos/AP-1/metalloproteinase 1 pathway. Involvement of transcription factor binding sites AP-1 and PEA-3.
pubmed:affiliation
Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't