Linked Life Data

17550983

Source:http://linkedlifedata.com/resource/pubmed/id/17550983

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-8-24
pubmed:abstractText
The production of chemokine stromal cell-derived factor (SDF)-1 is significantly higher in synovial fluid of patients with osteoarthritis and rheumatoid arthritis. Matrix metalloproteinase (MMP)-13 may contribute to the breakdown of articular cartilage during arthritis. Here, we found that SDF-1alpha increased the secretion of MMP-13 in cultured human chondrocytes, as shown by reverse transcriptase-polymerase chain reaction, Western blot, and zymographic analysis. SDF-1alpha also increased the surface expression of CXCR4 receptor in human chondrocytes. CXCR4-neutralizing antibody, CXCR4-specific inhibitor [1-[[4-(1,4,8,11-tetrazacyclotetradec-1-ylmethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane (AMD3100)], or small interfering RNA against CXCR4 inhibited the SDF-1alpha-induced increase of MMP-13 expression. The transcriptional regulation of MMP-13 by SDF-1alpha was mediated by phosphorylation of extracellular signal-regulated kinases (ERK) and activation of the activator protein (AP)-1 components of c-Fos and c-Jun. The binding of c-Fos and c-Jun to the activator protein (AP-1) element on the MMP-13 promoter and the increase in luciferase activity was enhanced by SDF-1alpha. Cotransfection with dominant-negative mutant of ERK2 or c-Fos and c-Jun antisense oligonucleotide inhibited the potentiating action of SDF-1alpha on MMP-13 promoter activity. Taken together, our results provide evidence that SDF-1alpha acts through CXCR4 to activate ERK and the downstream transcription factors (c-Fos and c-Jun), resulting in the activation of AP-1 on the MMP-13 promoter and contributing cartilage destruction during arthritis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
695-703
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17550983-Anti-HIV Agents, pubmed-meshheading:17550983-Arthritis, Rheumatoid, pubmed-meshheading:17550983-Cells, Cultured, pubmed-meshheading:17550983-Chemokine CXCL12, pubmed-meshheading:17550983-Chemokines, CXC, pubmed-meshheading:17550983-Chondrocytes, pubmed-meshheading:17550983-Dose-Response Relationship, Drug, pubmed-meshheading:17550983-Heterocyclic Compounds, pubmed-meshheading:17550983-Humans, pubmed-meshheading:17550983-Matrix Metalloproteinase 13, pubmed-meshheading:17550983-Osteoarthritis, pubmed-meshheading:17550983-RNA, Messenger, pubmed-meshheading:17550983-RNA, Small Interfering, pubmed-meshheading:17550983-Receptors, CXCR4, pubmed-meshheading:17550983-Stromal Cells, pubmed-meshheading:17550983-Synovial Fluid, pubmed-meshheading:17550983-Synovial Membrane
pubmed:year
2007
pubmed:articleTitle
Stromal cell-derived factor-1 induces matrix metalloprotease-13 expression in human chondrocytes.
pubmed:affiliation
Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't