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In the early stage, inflammation leads to the secretion of inflammatory and pro-degradative mediators, including cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-), lipid mediators such as prostaglandin E2 (PGE 2 ), and matrix metalloproteinases (MMPs) by macrophages and fibroblast-like synoviocytes 7,10

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