Fig. 1

Involvement of the synovium in OA pathophysiology. Products of cartilage breakdown released into the synovial fluid are phagocytosed by synovial cells, amplifying synovial inflammation. In turn, activated synovial cells in the inflamed synovium produce catabolic and pro-inflammatory mediators that lead to excess production of the proteolytic enzymes responsible for cartilage breakdown, creating a positive feedback loop. The inflammatory response is amplified by activated synovial T cells, B cells and infiltrating macrophages. To counteract this inflammatory response, the synovium and cartilage may produce anti-inflammatory cytokines. In addition to these effects on cartilage inflammation and breakdown, the inflamed synovium contributes to the formation of osteophytes via BMPs. ADAMTS a disintegrin and metalloproteinase with thrombospondin motifs, BMP bone morphogenetic protein, CXCL13 CXC-chemokine ligand 13, EGF endothelial growth factor, IL interleukin, IL-1Ra IL-1 receptor antagonist, LTB4, leukotriene B4, MMP matrix metalloproteinase, NAMPT nicotinamide phosphoribosyl transferase (visfatin), NO nitric oxide, OA osteoarthritis, PGE2 prostaglandin E2, TiMP tissue inhibitor of metalloproteinase, TNF tumour necrosis factor, VCAM-1, vascular cell adhesion molecule 1, VEGF vascular endothelial growth factor (Reprinted from [5] with permission from Macmillan Publishers Ltd)