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IL-1, IL-6, and TNF- can inhibit the synthesis of type II collagen (Col II) and glycosaminoglycans (GAGs,such as Chondroitin sulfate, Keratan sulfate, and Hyaluronic acid) while upregulating the production of cartilage-degrading enzymes such as matrix metalloproteinases (MMP-1, MMP-3, and MMP-13), thereby promoting ECM degradation (127) ( Figure 4 )