Plasma proteins take their toll on the joint in osteoarthritis

e view of osteoarthritis (OA) as strictly a non-infl am-ma tory joint disease has evolved as imaging and histo-pathological studies have demonstrated that synovial infl ammation is present in many patients, and importantly , is associated with increased pain, poorer joint function , and accelerated deterioration of joint struc tures. In the current article by Sohn and colleagues [1], the authors advance the understanding of how infl ammation may be initiated by demonstrating that certain plasma proteins present in OA synovial fl uids (SFs) can activate macro-phages via the innate immune receptor Toll-like receptor (TLR)-4. Th e authors began with a proteomic analysis, utilizing two-dimensional PAGE followed by liquid chromatography mass spectrometry, to survey proteins in SF from fi ve OA patients. Th e analysis identifi ed 108 proteins, many of which previously were shown to be increased in OA SF compared to normal, including proteins related to infl ammation and immunity and products of extracellular matrix degradation and remodeling [2]. Of these, 64 proteins were novel and included histone-related and macrophage-associated proteins, proinfl am ma tory receptors and proteins related to the proin fl am matory transcription factor nuclear factor kappa B. As the approach was not optimal for detection of small mole cules such as cytokines, they went on to perform multiplex bead-based immunoassays to measure cyto kines and chemokines involved in infl ammatory pro cesses and compared the levels in normal sera, OA and rheumatoid arthritis sera and OA and rheumatoid arthritis SF. In general, the levels in OA sera samples were only slightly higher than the normal levels and those in the rheumatoid arthritis sera were markedly higher. Some novel mediators were identifi ed by this comparison, including T cell attracting chemokine (CTAK) and IL-9, which were signifi cantly higher in the OA compared to the normal sera, supporting a role for T cells in OA infl ammation. Among the OA samples, multiple pro infl ammatory cytokines and chemokines were much higher in the SF compared to the sera, consistent with overproduction of these cyto-kines in the joints. Interestingly, they found that over one-third of proteins identifi ed in the proteomic screen of OA SF were plasma proteins. Th is is not unexpected, since SF is partially a plasma fi ltrate, but many of the plasma proteins were increased in OA compared to normal SF. Together with evidence that another plasma protein, fi brinogen, can incite …