Non-steroidal anti-inflammatory drugs protect against chondrocyte apoptotic death

Recent evidence suggests that the degradation of cartilage in osteoarthritis is characterized by chondrocyte apoptosis, but little is known about the molecular mechanisms involved or potential protective measures. In the present study, we used an immortalized chondrocyte cell line to explore the mechanisms of apoptotic chondrocyte cell death. We found that staurosporine-mediated chondrocyte death depended on the concentration and time of incubation and coincided with increased Bax:Bcl-X mRNA expression, cytochrome C release, and activation of caspase-3. Pre-treatment of the cultures with nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, or with ibuprofen, a non-selective COX-1/ COX-2 inhibitor, protected the chondrocytes against the staurosporine-mediated nuclear damage and cell death in a concentration-dependent manner (10^-12 to 10^-6 M). Cell protection coincided with inhibition of the staurosporine-mediated induction of caspase-3 activation. Notably, the selective COX-2 inhibitor NS-398 (10^-6 M, 24 hr pre-treatment) did not protect the cells against staurosporine-mediated apoptotic death. The data suggest that nimesulide and ibuprofen, in addition to their anti-inflammatory and analgesic benefits, may also have a protective effect in osteoarthritis through the inhibition of apoptosis in chondrocytes.