Osteoarthritis, an inflammatory disease: potential implication for the selection of new therapeutic targets.

Osteoarthritis (OA) is a well-known disease that is part of the aging process and also one of the most common diseases among mammals. Although this musculoskeletal disorder has been described in mammals of many ages, having been reported in Egyptian mummies and in dinosaurs, its exact etiology is far from being fully understood. With the graying of the world population, it is of the utmost importance to find out more about the pathogenesis of the disease and thus allow the discovery of new treatments to stop or prevent its progression. A number of risk factors have lately been identified (1). Mechanical factors, among others, are likely to play a very important role in the initiation of the disease process. Endogenous factors such as type II collagen mutation or dysplastic conditions are also known to be involved in initiating the OA process (2). There is now strong evidence that the structural changes globally observed in OA are due to a combination of factors, ranging from the mechanical to the biochemical (3,4). The disease process affects not only the cartilage, but also the entire joint structure, including the synovial membrane, subchondral bone, ligaments, and periarticular muscles. In OA synovium, the inflammatory changes that take place include synovial hypertrophy and hyperplasia with an increased number of lining cells, and also an infiltration of the sublining tissue with a mixed population of inflammatory cells. In patients with severe disease, the extent of inflammation can sometimes reach that observed in rheumatoid arthritis (RA) patients at the clinical stage (5,6). Some degree of synovitis has also been reported in even the early stages of the disease (7). Synovial inflammation is clearly reflected in many of the signs and symptoms of OA, including joint swelling and effusion, stiffness, and sometimes redness, particularly at the level of the proximal interphalangeal (PIP) and distal interphalangeal (DIP) joints.