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KMID : 0923620060060040204
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Immune Network
2006 Volume.6 No. 4 p.204 ~ p.209
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Src Kinase Regulates Nitric Oxide-induced Dedifferentiation and Cyclooxygenase-2 Expression in Articular Chondrocytes via p38 Kinase-dependent Pathway
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Yu Seon-Mi
Lee Won-Kil
Yoon Eun-Kyung
Lee Ji-Hye
Kim Song-Ja
Lee Sun-Ryung
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Abstract
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Background: Nitric oxide (NO) in articular chondrocytes regulates dedifferentiation and inflammatory responses by modulating MAP kinases. In this study, we investigated whether the Src kinase in chondrocytes regulates NO-induced dedifferentiation and cyclooxygenase-2 (COX-2) expression.
Methods: Primary chondrocytes were treated with various concentrations of SNP for 24 h. The COX-2 and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin E2 (PGE2) was determined by using a PGE2 assay kit. Expression and distribution of p-Caveolin and COX-2 in rabbit articular chondrocytes and cartilage explants were determined by immunohistochemical staining and immunocytochemical staining, respectively.
Results: SNP treatment stimulated Src kinase activation in a dose-dependent manner in articular chondrocytes. The Src kinase inhibitors PP2 [4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine], a significantly blocked SNP-induced p38 kinase and caveolin-1 activation in a dose-dependent manner. Therefore, to determine whether Src kinase activation is associated with dedifferentiation and/or COX-2 expression and PGE2 production. As expected, PP2 potentiated SNP-stimulated dedifferentiation, but completely blocked both COX-2 expression and PGE2 production. And also, levels of p-Caveolin and COX-2 protein expression were increased in SNP-treated primary chondrocytes and osteoarthritic and rheumatoid arthritic cartilage, suggesting that p-Caveolin may play a role in the inflammatory responses of arthritic cartilage.
Conclusion: Our previously studies indicated that NO caused dedifferentiation and COX-2 expression is regulated by p38 kinase through caveolin-1 (1). Therefore, our results collectively suggest that Src kinase regulates NO-induced dedifferentiation and COX-2 expression in chondrocytes via p38 kinase in association with caveolin-1. (Immune Network 2006;6(4):204-210)
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KEYWORD
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Src kinase, Caveolin-1, Dedifferentiation, COX-2, p38 kinase
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