Abstract
Pro-inflammatory cytokines are considered to play a major role in osteoarthritis (OA), yet so far, the specific cytokines involved in the pathology of OA have not been identified. Oncostatin M (OSM) is a cytokine from the interleukin 6 (IL-6) family that has been shown to be elevated in synovial fluid of most rheumatoid arthritis (RA) patients, but only in a limited subset of OA patients. Little is known about OSM in the different joint tissues during OA and how its expression correlates with hallmarks of disease. Here, we mapped OSM expression in the joint tissues of two rat models of arthritis: an acute inflammatory model and an instability-induced osteoarthritic model. OSM expression was correlated with hallmarks of OA, namely cartilage damage, synovitis, and osteophyte formation. Reanalysis of an existing dataset on cytokine profiling of OA synovial fluid was performed to assess pattern differences between patients positive and negative for OSM. In the inflammatory model, OSM expression correlated with synovitis and osteophyte formation but not with cartilage damage. On the contrary, in the instability model of OA, an increase in synovitis, cartilage damage, and osteophyte formation was observed without changes in OSM expression. In line with these findings, synovial fluid of OA patients with detectable OSM contained higher levels of other inflammatory cytokines, namely interferon gamma (IFN-γ), IL-1α and tumor necrosis factor alpha (TNF-α), likely indicating a more inflammatory state. Taken together these data indicate OSM might play a prominent role in inflammatory phenotypes of OA.
Highlights
Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability and morbidity worldwide [1,2]
We evaluated whether Oncostatin M (OSM) expression is associated with hallmarks of disease, such as cartilage damage, synovial inflammation, and osteophyte formation in these models
To map the presence of OSM in different phenotypes of joint diseases, OSM expression was evaluated by immunohistochemistry in two mouse models: inflammatory arthritis (PGPS model) and degenerative OA (ACLT) model
Summary
Osteoarthritis (OA) is the most prevalent musculoskeletal disorder and a leading cause of disability and morbidity worldwide [1,2]. Tumor necrosis factor alpha (TNF-α) and interleukin 1 (IL-1) are two of the most studied mediators in OA In vitro, they have been shown to increase production of matrix-degrading enzymes and other inflammatory mediators such as MMPs 1, 3, and 13, ADAMTSs 4 and 5, and IL-6 in chondrocytes [3]. Several clinical trials targeting these cytokines have shown no effect [5,6,7], contrasting the clear alleviation of symptoms in RA upon their inhibition These observations may be in part explained by the fact that in the OA joint the levels of these mediators are lower than those of their natural inhibitors, such as IL-1 receptor antagonist and soluble TNF-α receptors [8,9]
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