Synovial fluid levels of tumor necrosis factor α and oncostatin M correlate with levels of markers of the degradation of crosslinked collagen and cartilage aggrecan in rheumatoid arthritis but not in osteoarthritis

Abstract

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.

In Human Macrophages the Complement Component C5a Induces the Expression of Oncostatin M via AP-1 Activation

“…Elevated levels of OSM have been found at sites of inflammation, and OSM has been shown to regulate the expression of other inflammatory mediators such as IL-6. 35,36 In that respect and in the light of our results presented here it should also be emphasized that OSM as well as C5a have been recently implicated in the pathology of inflammatory joint destruction. 37,38 Thus we hypothesize that this link between the complement system and the gp130 receptor cytokine family might potentially impact on the pathology of inflammatory disease.…”

Adenoviral Gene Transfer of Interleukin-1 in Combination with Oncostatin M Induces Significant Joint Damage in a Murine Model

“…Both IL-1 and OSM alone have been reported to induce joint inflammation and cartilage destruction in vitro and in vivo, and elevated levels of these two cytokines in synovial fluid of RA patients correlate with disease activity and destruction of cartilage and bone. [2][3][4][5]7,8 The present study demonstrates for the first time that IL-1 in combination with OSM induces marked joint inflammation, synovial hyperplasia, pannus formation, and cartilage/bone destruction in a murine model, which are all hallmarks of the pathological changes seen in RA. Specifically, this combination causes dramatic proteoglycan and collagen loss as reported previously in cartilage explant studies, 7,17 and this is associated with elevated levels of MMP expression.…”

“…OSM has been localized to the macrophages within RA synovium, 7 and elevated synovial fluid levels of OSM 7,8 correlate with markers of joint inflammation and cartilage destruction in RA. 2 In experimental animals, intraarticular delivery of human OSM or recombinant adenovirus vectors overexpressing murine OSM (AdmOSM) cause synovial inflammation and structural damage. 9 -11 Blockade of OSM ameliorates joint inflammation and cartilage damage in collagen-induced arthritis.…”

Immunopathological mechanisms in dogs with rupture of the cranial cruciate ligament

“…1). Joint aspirates from human patients with arthritis often contain wear particles, for example, collagen, proteoglycan, bone, uric acid, fibronectin, crystals and other, as yet unidentified, materials (Evans et al, 1984;Xie et al, 1992;Lohmander et al, 1993Lohmander et al, , 1994Manicourt et al, 2000;Nalbant et al, 2003). Some of these wear particles have also been identified in the SF of dogs with arthropathy (Arican et al, 1994;Innes et al, 1998;Chu et al, 2002).…”