CHONDROCYTE APOPTOSIS AND NITRIC-OXIDE PRODUCTION DURING EXPERIMENTALLY-INDUCED OSTEOARTHRITIS

Objective. Chondrocytes produce nitric oxide (NO) and undergo apoptosi s in response to exogenous NO. This study sought to examine the relati onship between NO synthesis, chondrocyte apoptosis, and the developmen t of cartilage degradation during experimental osteoarthritis (OA). Me thods. OA was induced in rabbits by anterior cruciate ligament transec tion (ACLT), Knees were harvested after 4 weeks and assessed for OA se verity and chondrocyte apoptosis, Conditioned media from cultured cart ilage explants were analyzed for nitrite content. Cartilage sections w ere analyzed by immunohistochemistry for the presence of nitrotyrosine . Results. All ACLT knees demonstrated osteoarthritic changes, Conditi oned media from ACLT cartilage organ cultures contained higher levels of nitrite as compared with cartilage samples from the nonoperated sid e or from rabbits that had not received ACLT, Cultures of specific are as of cartilage from ACLT knees showed high levels of NO production in the medial femoral and medial tibial cartilage. Approximately 28.7% o f chondrocytes isolated from ACLT cartilage and 6.7% of chondrocytes f rom cartilage of the nonoperated side underwent apoptosis, In situ sta ining demonstrated apoptotic cells in the superficial and middle zones of ACLT cartilage. A high number of apoptotic cells was present at th e pannus-cartilage junction. In control cartilage, the superficial zon e contained a small number of cells in apoptosis, The prevalence of ap optotic cells was significantly correlated with the levels of nitrite production and OA grade. Conclusion, These observations suggest that, during the early phases of OA, NO production may lead to chondrocyte a poptosis, and that both events contribute to the pathogenesis of carti lage degradation. Inhibitors of NO synthesis and chondrocyte apoptosis may therefore be of therapeutic value after cartilage injury and in p atients with OA.