Inhibition of XXXX apoptotic signaling by @entity379 in @entity1 osteoarthritic chondrocytes is associated with increased expression of @entity8186 inhibitory protein.

@entity1 @entity1182 @entity522 @entity571 @entity42977 @entity1197 @entity8186 @entity10204 @entity12 @entity379
OBJECTIVE: Cartilage @entity10204 during @entity571 ( @entity571 ) has been linked to an increased rate of apoptosis of chondrocytes, the only cell type resident in the cartilage. In addition, the @entity1197 - @entity12 (the Fas system) has emerged as one of the major pathways of cell death in the cartilage. We undertook the present study to investigate the role of @entity379 ( @entity379 ) in the regulation of the Fas system by analyzing the modulation of intracellular signaling molecules ( @entity8186 inhibitory protein [ @entity1182 ] and @entity42977 ) in primary cultures of @entity1 @entity571 chondrocytes. METHODS: @entity1197 -induced apoptotic death of @entity1 @entity571 chondrocytes was analyzed in the presence or absence of @entity379 using cell death immunoassay for apoptosis, real-time polymerase chain reaction for @entity1182 and @entity8186 expression, Western blotting for @entity1182 , and proteolytic activity for @entity42977 . RESULTS: @entity1197 -induced apoptotic death of @entity1 @entity571 chondrocytes was strongly counteracted by @entity379 treatment, although the surface expression of @entity1197 was slightly up-regulated by this cytokine. The messenger RNA (mRNA) expression of @entity1182 and @entity8186 , mediators involved in @entity1197 signaling, revealed that @entity1182 expression in @entity1 @entity571 chondrocytes was significantly up-regulated (2-fold increase) by @entity379 treatment. Moreover, the @entity1182 : @entity8186 mRNA ratio increased significantly. @entity1182 up-regulation by @entity379 was confirmed at the protein level. @entity8186 and @entity522 proteolytic activities, both induced in these cells by stimulation with anti- @entity1197 , were also significantly down-modulated by @entity379 . CONCLUSION: These findings suggest that @entity379 impairs @entity1197 -mediated signaling and apoptotic death in @entity1 chondrocytes. Its mechanism of action involves down-regulation of @entity8186 and @entity522 activities and increased expression of the antiapoptotic protein @entity1182 , suggesting an interesting mechanism for the inhibition of chondrocyte apoptosis.
