This open access paper discusses current views on the degree to which osteoarthritis is driven by inflammation, as is the case for many other age-related diseases. With aging the immune system declines into a malfunctioning state of chronic inflammation, ever more active while also ever less effective at the tasks of destroying pathogens and errant cells. In young people, inflammation in short bursts is a necessary part of the immune response, but in the old it becomes a consistent destructive process, gnawing away at the proper function of organs and systems in the body and brain. Addressing this in some way, perhaps through an adaptation of the immune destruction and recreation approach taken for some autoimmune diseases, should be broadly beneficial.
Affecting approximately 3.8% of the global population, osteoarthritis (OA) is regarded as a prevalent cause of morbidity and disability worldwide. OA shows many disease characteristics, such as cartilage degradation, moderate synovial inflammation, pain, alteration of bony structure, and impaired mobility. However, despite the severity of the disease, relatively little is known about its exact etiology. Recent compelling investigations have attributed the onset of OA to various person-level factors such as age, sex, obesity, and diet and joint-level factors such as injury, malalignment, and abnormal joint loading. Although more and more researchers have recently presented hypotheses concerning the involvement of these factors in OA, especially for person-level factors, few of their hypotheses have been demonstrated experimentally, and some have even been challenged by the latest observational studies and clinical trials.
Of the several factors potentially involved in the pathogenesis of OA, T cell-mediated immune responses and their influence on the biology of OA are the focus of this review. The scientific community once understood OA to be induced by mechanical stress in the form of cartilage destruction, with minimal if any involvement of immune responses. Thus, OA was regarded as a non-inflammatory disease, in contrast with rheumatoid arthritis (RA), an inflammatory disease. However, recent studies suggest that at least in certain patients, OA is an inflammatory disease; patients have frequently been found to exhibit inflammatory infiltration of synovial membranes. Most recent studies have shown that the number of inflammatory cells in the synovial tissue is lower in patients with OA than in patients with RA, but higher than that in healthy subjects. Indeed, little difference has been found in the percentages of T cells, B cells, and natural killer cells in the peripheral blood between patients with OA and RA. The similarity of the immune cell profiles of RA and OA and suggested that abnormalities in T cells may also contribute to the pathogenesis of OA.
Further experiments indicated that inflammation in OA is anatomically restricted and varies in intensity. The synovial membranes in regions rimming the cartilage of OA patients, which contain T cells bordered by B lymphocytes and plasma cells, showed a pronounced inflammatory response. In contrast, only a few infiltrating lymphocytes were observed in the synovial membranes taken from macroscopically non-inflamed areas in OA patients. This may explain the suggestion made by some researchers that immune responses are not involved in the pathogenesis of OA. When synovial samples from patients with knee OA were analyzed, the synovial lining cells showed strong immunoreactivity and phagocytic potential with cluster of differentiation (CD) 68 antibodies. These findings suggested that macrophages may be associated with the pathogenesis of knee OA. Of 20 osteoarthritic synovial membranes, 5 showed lymphoid follicles containing T cells, B cells, and macrophages, and 10 (including the latter five) displayed a diffuse cellular infiltrate containing T and B cells, macrophages, and granulocytes. These results suggested that B cells and granulocytes may also be involved in the pathogenesis of knee OA.