The roles of catabolic factors in the development of osteoarthritis.

Osteoarthritis (OA) is the most prevalent disease of articular joints characterized by joint space narrowing on X-ray, joint pain, and a loss of joint function through progressive cartilage degradation and intermittent synovial inflammation. Current in vitro models of OA are often monolayer cultured primary cells exposed to high concentrations of cytokines or chemokines, usually IL-1β or TNF-α. IL-1β could play a role in the early progression or even initiation of OA as evidenced by many of the in vitro studies. However, the inconsistent or outright lack of detectable IL-1β combined with high concentrations of the natural inhibitor IL-1Ra in the OA synovial fluid makes the idea of OA being IL-1β-driven questionable. Further, other stimulants, including IL-6 and matrix fragments, have been shown in vitro to cause many of the effects seen in OA at relevant concentrations found in the OA synovial fluid. More work with these stimulants and IL-1β-independent models needs to be done. Concurrently, research should be conducted with patients with OA as early as possible in the progression of their disease to be able to potentially identify, target, and treat the initiation of the disease.