beta-catenin regulates expression of cyclooxygenase-2 in articular chondrocytes

Abstract

Pro-inflammatory cytokine such as interleukin (IL)-1β causes inflammation of articular cartilage via induction of cyclooxygenase (COX)-2 expression. We investigated in this study the role of β-catenin in the IL-1β regulation of COX-2 expression in articular chondrocytes. IL-1β increased expression of COX-2 and induced accumulation and nuclear translocation of transcriptionally competent β-catenin. Inhibition of β-catenin degradation by the treatment of cells with LiCl or proteasome inhibitor stimulated expression of COX-2, indicating that transcriptionally active β-catenin is sufficient to induce COX-2 expression. This was demonstrated further by the observation that ectopic expression of transcriptionally competent β-catenin stimulated expression of COX-2. Levels of β-catenin and COX-2 protein were increased in osteoarthritic and rheumatoid arthritic cartilage, suggesting that β-catenin may play a role in the inflammatory responses of arthritic cartilage. Taken together, our data suggest that accumulation of transcriptionally active β-catenin contributes to the expression of COX-2 in articular chondrocytes. © 2002 Elsevier Science (USA). All rights reserved.