Linked Life Data

18437285

Source:http://linkedlifedata.com/resource/pubmed/id/18437285

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-8-6
pubmed:abstractText
We previously reported that synovial fibroblast-like cells (SFs) can be differentiated into chondrocytes through activin receptor-like kinase (ALK) 3 activation. The aim of this study was to clarify the effect and signaling pathways of tumor necrosis factor (TNF)-alpha on the chondrogenic differentiation of SFs. Primary SFs from patients with rheumatoid arthritis (RA) were treated with recombinant human bone morphogenetic protein-2 or transduced with a constitutively active mutant of the ALK3 gene (ALK3CA) with or without TNF-alpha, and then cultured in pellets. Expression of chondrocyte-specific genes was analyzed by real-time polymerase chain reaction or by histological analysis. Inhibitors of mitogen-activating protein kinase (MAPK) pathways or adenovirus vectors carrying a dominant-negative mutant of the IkappaB kinase 2 gene (AxIKK2DN) were used to analyze the signaling pathways of TNF-alpha. Expression of chondrocyte-specific genes was induced in SFs either by rhBMP-2 treatment or by ALK3CA transduction, which was strongly suppressed by TNF-alpha treatment. TNF-alpha markedly increased the p38 MAPK pathways in SFs, and inhibition of p38 MAPK activation partially restored the inhibitory effect of TNF-alpha on the chondrogenic differentiation of SFs. Combination therapy BMP-2 and anti-TNF-alpha agents especially targeting p38 MAPK might be a good approach to stimulating neochondrogenesis in the damaged joints in RA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1439-7595
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
366-78
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Tumor necrosis factor-alpha inhibits chondrogenic differentiation of synovial fibroblasts through p38 mitogen activating protein kinase pathways.
pubmed:affiliation
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't