Introduction The aim of this study was to examine IL-17A in patients, following anti-TNF-α therapy and the effect of IL-17A on matrix turnover and cartilage degradation.

Serum amyloid A (A-SAA), an acute-phase protein with cytokine-like properties, is expressed at sites of inflammation. This study investigated the effects of A-SAA on chemokine-regulated migration and angiogenesis using rheumatoid arthritis (RA) cells and whole-tissue explants in vitro, ex vivo, and in vivo. A-SAA levels were measured by real-time PCR and ELISA. IL-8 and MCP-1 expression was examined in RA synovial fibroblasts, human microvascular endothelial cells, and RA synovial explants by ELISA. Neutrophil transendothelial cell migration, cell adhesion, invasion, and migration were examined using transwell leukocyte/monocyte migration assays, invasion assays, and adhesion assays with or without anti–MCP-1/anti–IL-8. NF-κB was examined using a specific inhibitor and Western blotting. An RA synovial/SCID mouse chimera model was used to examine the effects of A-SAA on cell migration, proliferation, and angiogenesis in vivo. High expression of A-SAA was demonstrated in RA patients (p < 0.05). A-SAA induced chemokine expression in a time- and dose-dependent manner (p < 0.05). Blockade with anti-scavenger receptor class B member 1 and lipoxin A4 (A-SAA receptors) significantly reduced chemokine expression in RA synovial tissue explants (p < 0.05). A-SAA induced cell invasion, neutrophil–transendothelial cell migration, monocyte migration, and adhesion (all p < 0.05), effects that were blocked by anti–IL-8 or anti–MCP-1. A-SAA–induced chemokine expression was mediated through NF-κB in RA explants (p < 0.05). Finally, in the RA synovial/SCID mouse chimera model, we demonstrated for the first time in vivo that A-SAA directly induces monocyte migration from the murine circulation into RA synovial grafts, synovial cell proliferation, and angiogenesis (p < 0.05). A-SAA promotes cell migrational mechanisms and angiogenesis critical to RA pathogenesis.

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Conclusion. These data suggest that OSM promotes angiogenesis and endothelial cell migration and potentiates the effects of IL-1␤ in promoting extracellular matrix turnover and human cartilage degradation. Furthermore, the induction of VEGF in cocultures supports the hypothesis of a link between angiogenesis and cartilage degradation.Rheumatoid arthritis (RA) is a chronic disease characterized by synovial tissue proliferation and articular cartilage degradation (1,2). In RA, angiogenesis is an early event required for pannus development, enabling activated monocytes to enter the synovium via endothelial cells by active recruitment (3). The new vessels support expansion of the synovial pannus over the cartilage, facilitating RA synovial fibroblast (RASF) invasion and cartilage degradation by proteolytic cleavage of both aggrecan and collagen (4). This process depends on cytokines and growth factors to stimulate cell survival, proliferation, and extracellular matrix (ECM) degradation (5). Erosion is characterized by a loss of ECM by overexpression of matrix metalloproteinSupported by the Health Research Board of Ireland.

Objective. To investigate the relationship between acute-phase serum amyloid A (A-SAA) and joint destruction in inflammatory arthritis.Methods. Serum A-SAA and C-reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), and levels of matrix metalloproteinase 1 (MMP-1), MMP-2, MMP-3, MMP-9, MMP-13, tissue inhibitor of metalloproteinases 1 (TIMP-1), vascular endothelial growth factor (VEGF), and type I and type II collagengenerated biomarkers C2C and C1,2C were measured at 0-3 months in patients with inflammatory arthritis commencing anti-tumor necrosis factor ␣ (anti-TNF␣) therapy and were correlated with 1-year radiographic progression. The effects of A-SAA on MMP/TIMP expression on RA fibroblast-like synoviocytes (FLS), primary human chondrocytes, and RA/psoriatic arthritis synovial explant cultures were assessed using real-time polymerase chain reaction, enzyme-linked immunosorbent assay, antibody protein arrays, and gelatin zymography.Results. Serum A-SAA levels were significantly (P < 0. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are inflammatory autoimmune disorders characterized by joint destruction and disability (1). Synovial inflammation, which occurs through angiogenesis, leu-