Immune Netw.  2006 Sep;6(3):117-122. 10.4110/in.2006.6.3.117.

p38 Kinase Regulates Nitric Oxide-induced Dedifferentiation and Cyclooxygenase-2 Expression of Articular Chondrocytes

• Yu SM
• Cheong SW
• Cho SR
• Kim SJ

• KMID: 1808155
• DOI: http://doi.org/10.4110/in.2006.6.3.117

Abstract

BACKGROUND: Caveolin, a family of integral membrane proteins are a principal component of caveolae membranes. In this study, we investigated the effect of p38 kinase on differentiation and on inflammatory responses in sodium nitroprusside (SNP)- treated chondrocytes.
METHODS
Rabbit articular chondrocytes were prepared from cartilage slices of 2-week-old New Zealand white rabbits by enzymatic digestion. SNP was used as a nitric oxide (NO) donor. In this experiments measuring SNP dose response, primary chondrocytes were treated with various concentrations of SNP for 24 h. The time course of the SNP response was determined by incubating cells with 1 mM SNP for the indicated time period (0~24 h). The cyclooxygenase-2 (COX-2) and type II collagen expression levels were determined by immunoblot analysis, and prostaglandin E2 (PGE2) assay was used to measure the COX-2 activity. The tyrosine phosphorylation of caveolin-1 was determined by immunoblot analysis and immunostaining.
RESULTS
SNP treatment stimulated tyrosine phosphorylation of caveolin-1 and activation of p38 kinase. SNP additionally caused dedifferentiation and inflammatory response. We showed previously that SNP treatment stimulated activation of p38 kinase and ERK-1/-2. Inhibition of p38 kinase with SB203580 reduced caveolin-1 tyrosine phosphorylation and COX-2 expression but enhanced dedifferentiation, whereas inhibition of ERK with PD98059 did not affect caveolin-1 tyrosine phosphorylation levels, suggesting that ERK at least is not related to dedifferentiation and COX-2 expression through caveolin-1 tyrosine phosphorylation.
CONCLUSION
Our results indicate that SNP in articular chondrocytes stimulates dedifferentiation and inflammatory response via p38 kinase signaling in association with caveolin-1 phosphorylation.

Keyword

SNP; caveolin-1; dedifferentiation; inflammatory response; p38 kinase

MeSH Terms

Cartilage
Caveolae
Caveolin 1
Chondrocytes*
Collagen Type II
Cyclooxygenase 2*
Digestion
Dinoprostone
Humans
Membrane Proteins
Membranes
Nitric Oxide
Nitroprusside
Phosphorylation
Phosphotransferases*
Rabbits
Tissue Donors
Tyrosine
Caveolin 1
Collagen Type II
Cyclooxygenase 2
Dinoprostone
Membrane Proteins
Nitric Oxide
Nitroprusside
Phosphotransferases
Tyrosine