Objective. To compare synovial fluid (SF) levels of oncostatin M (OSM), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to determine which correlate best with SF levels of antigenic keratan sulfate (Ag KS), a marker of aggrecan catabolism, and pyridinium crosslinks, markers of the degradation of mature collagen molecules. Methods. SF was drawn from the knee joints of patients with RA (n 31) or OA (n 31). Levels of Ag KS, D-pyridinoline (D-Pyr), pyridinoline (Pyr), OSM, TNF, and IL-6 were measured by enzyme-linked im-munosorbent assay. Results. RA patients had higher median SF levels of OSM, TNF, IL-6, and Pyr, but a lower median level of D-Pyr, than OA patients. In both groups, IL-6 levels correlated positively with those of OSM and TNF. However, the correlation between levels of OSM and TNF was only significant in the RA group. Ag KS and Pyr levels correlated positively in RA but not in OA. The correlation between TNF and Ag KS was positive in RA and negative in OA. Further, in RA, OSM and IL-6 levels correlated strongly with Pyr and Ag KS levels but not with D-Pyr levels, while there were no strong correlations in OA for OSM or IL-6 levels with Pyr, Ag Ks, or D-Pyr levels. Conclusion. This in vivo study suggests that TNF and other proinflammatory cytokines are involved in the up-regulation of the coordinated degradation of cartilage aggrecan and collagen in RA. Further, OSM may act synergistically with other proinflamma-tory cytokines in up-regulating the production of me-talloproteinases by chondrocytes in rheumatoid joints. Fibril-forming collagens (types I-III, V, and XI) are the most abundant collagenous components of joint structures, where they form a meshwork of crosslinked fibrils that give the tissues most of their tensile strength (1). The 2 major forms of mature crosslinking residues found in polymers of fibrillar collagen are hydroxyly-sylpyridinoline, also termed pyridinoline (Pyr) and ly-sylpyridinoline, also referred to as deoxypyridinoline (D-Pyr) (2). Bone collagen is the primary repository of D-Pyr, while collagen from cartilage, meniscus, tendon, and joint capsule is rich in Pyr (2,3). In articular cartilage, crosslinked collagenous fibrils (types II, IX, and XI) also contribute indirectly to the resilience and compressive stiffness of the tissue by entrapping in an underhydrated form viscoelastic aggre-can molecules bearing numerous anionic chondroitin sulfate and keratan sulfate (KS) side chains (4,5). The mechanisms that regulate the normal turnover of these key functional elements and their degradation in arthrit-ides are still poorly understood. In recent years, the quantification of "molecular markers of joint metabo-Supported by the fonds de développement scientifique of the Université Catholique de Louvain, fund 3.4597.98 for Medical Scientific Research (Belgium), and grants AG-04736 and AR-39239 from the NIH, Bethesda, MD.
