Studies have suggested that HIF-2 directly regulates catabolic factors such as MMP1, MMP3, MMP9, MMP13, ADAMTS4, NOS2, and PTGS2 to destroy cartilage in osteoarthritis, while the application of the specificity protein 1 (SP1) inhibitor Mithramycin A (MitA) could reduce the expression of HIF-2, thereby reducing the destruction of cartilage in osteoarthritis [48,83] have shown that HIF-1α suppresses the NF-κB-HIF-2α axis to regulate the growth of articular cartilage [84]. This evidence concerns the gene MMP3 and osteoarthritis.