Altered gene expression during nimesulide-mediated inhibition of apoptotic death in human chondrocytes.

Overview

We previously found that the cyclooxygenase (COX)-2 preferential inhibitor nimesulide protects rodents' chondrocytes against apoptotic death in vitro. In the present study, we found that nimesulide also reduces staurosporine-mediated apoptotic death in human chondrocytes in vitro. Using cDNA microarrays, we explored alterations in gene expression during human chondrocytic apoptosis, and the influence of nimesulide therapy on these changes. Based on their known biologic activities, candidate gene products with altered expression were assigned to clusters of biological functions and mechanisms, and analysed for specific sets of alterations. We found that the expression of genes involved in cell proliferation is differentially regulated during staurosporine-mediated apoptotic death in human chondrocytes. Treatment with nimesulide reversed the staurosporine-mediated effects on these gene products during protection against apoptosis. The study suggests that nimesulide, in addition to its analgesic effect, may confer chondroprotection through mechanisms beyond classical COX inhibition.