TNF and arthritic joint disease: 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