Relevance of Nrf2 and heme oxygenase-1 in articular diseases

Joint conditions pose an important public health problem as they are a leading cause of pain, functional limitation and physical disability. Oxidative stress is related to the pathogenesis of many chronic diseases affecting the joints such as rheumatoid arthritis and osteoarthritis. Cells have developed adaptive protection mechanisms to maintain homeostasis such as nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) which regulates the transcription of many genes involved in redox balance, detoxification, metabolism and inflammation. Activation of Nrf2 results in the synthesis of heme oxygenase-1 (HO-1) leading to the formation of a number of bioactive metabolites, mainly CO, biliverdin and bilirubin. Ample evidence supports the notion that Nrf2 and HO-1 can confer protection against oxidative stress and inflammatory and immune responses in joint tissues. As a consequence, this pathway may control the activation and metabolism of articular cells to play a regulatory role in joint destruction thus offering new opportunities for better treatments. Further studies are necessary to identify improved strategies to regulate Nrf2 and HO-1 activation in order to enable the development of drugs with therapeutic applications in joint diseases.