Increased production of different MMPs was observed in the synovial fluid and synovial fibroblasts in inflamed joints.78 Macrophage migration inhibitory factor is mainly produced by macrophages in response to various inflammatory stimuli and has been shown to upregulate expression of MMP-1 and -3 in cultured synovial fibroblasts from RA patients,79 while MMP-9 and MMP-13 expression in RA joint fluid is significantly associated with VEGF and might be involved in angiogenesis.80 Proteinases are also involved in joint destruction in OA,81 spondyloarthropathies,82 SSc,83 and SLE.84 This evidence concerns the gene VEGFA and rheumatoid arthritis.