Purpose of review: Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of synovial joints.
Recent findings: Inflammation was seen as the key component promoting synovitis as well as progression of cartilage and bone destruction in osteoarthritis. Thus, metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants and even complement, all appear to play major roles in osteoarthritis pathophysiology. Immune-mediated inflammation involving T cells and B cells as well as macrophages is now considered a common finding in osteoarthritis synovial tissue. Many experimental and clinical analyses showed that the proinflammatory cytokines, which stimulate matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motif gene transcription in normal and osteoarthritis human chondrocyte cultures, are also present at significantly elevated levels in the synovial fluid of osteoarthritis patients compared with nonarthritic synovial fluids.
Summary: Human osteoarthritis is a systemic musculoskeletal disorder involving activation of innate and adaptive immune systems accompanied by inflammation exemplified by the elevated production of proinflammatory cytokines, which play a significant role in the progression of the disease. The future of novel therapies for osteoarthritis should consider developing drug development strategies designed to inhibit proinflammatory cytokine-induced signal transduction. These strategies have been successful in the development of drugs for the treatment of rheumatoid arthritis.