The study investigated the oxidative damage and antioxidant capacity in the cartilage of patients with osteoarthritis (OA) undergoing knee surgery to elucidate if oxidative stress due to oxygen free radical-induced genomic instability is implicated in the progression of this condition. They used cartilage samples of the intact and degenerative regions of the OA cartilage explants to detect the marker of oxidative damage nitrotyrosine as well as the replicative potential of the cells, telomere instability and production of proteoglycan aggrecan glycosaminoglycan (GAG) both under treatment with reactive oxygen species or an antioxidant (vitamin C). The degenerative regions showed a lower antioxidant capacity and stronger staining of nitrotyrosine compared to the intact regions of the same explant, indicative of a correlation between oxidative damage and cartilage degeneration. On the other hand, antioxidant therapy revealed a propensity to extend the replicative lifespan of cultured chondrocytes. This suggests the role of oxidative stress on the cartilage aging that causes the development of OA.