The role of reactive oxygen species in homeostasis and degradation of cartilage.

The metabolism of cells in articular joint tissues in normal and pathological conditions is subject to a complex environmental control. In addition to soluble mediators such as cytokines and growth factors, as well as mechanical stimuli, reactive oxygen species (ROS) emerge as major factors in this regulation. ROS production has been found to increase in joint diseases, such as osteoarthritis and rheumatoid arthritis, but their role in joint diseases initiation and progression remains questionable. This review is focused on the role of ROS, mainly nitric oxide, peroxynitrite and superoxide anion radicals, in the signaling mechanisms implied in the main cellular functions, including synthesis and degradation of matrix components. The direct effects of ROS on cartilage matrix components as well as their inflammatory and immunomodulatory effects are also considered. Some intracellular signaling pathways are redox sensitive and ROS are involved in the regulation of the production of some biochemical factors involved in cartilage degradation and joint inflammation. Further, ROS may cause damage to all matrix components, either by a direct attack or indirectly by reducing matrix components synthesis, by inducing apoptosis or by activating latent metalloproteinases. Finally, we have highlighted the uncoupling effect of ROS on tissue remodeling and synovium inflammation, suggesting that antioxidant therapy could be helpful to treat structural changes but not to relieve symptoms. This review of the literature supports the concept that ROS are not only deleterious agents involved in cartilage degradation, but that they also act as integral factors of intracellular signaling mechanisms. Further investigation is required to support the concept of antioxidant therapy in the management of joint diseases.