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TNF- can induce the proliferation of fibroblast-like synoviocytes (FLS) and synovial cells by activating nuclear factor kappa-B (NF-B) and extracellular regulated protein kinases (Erk)-1/2-E26 transformation-specific (ETS)-1 signaling pathway, respectively (70, 71), resulting in the secretion of a variety of inflammatory mediators like IL-6, matrix metalloproteinases (MMP)-1, and MMP-3 to increase inflammation (72)