HIF-2α is the cartilage catabolism regulator working as a matrix-degrading enzyme and inflammation mediator (IL-1, IL-6, and TNF-α), increasing the expression of proteolytic enzymes and MMPs (Matrix Metalloproteinases), accelerating cartilage destruction and causing chondrocyte hypertrophy, all of which play the role in the arthritis development.36 Here, TNF is linked to Arthritis.