By activating the nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), and Toll-like receptor (TLR) signaling pathways, these proinflammatory cytokines can induce disc degeneration by promoting catabolic enzymes, such as a disintegrin and metalloproteinase with thrombospondin motif- (ADAMTS-) 4 and -5 and MMP-1, -2, -3, -4, -13, and -14, and decreasing anabolic ECM proteins, such as aggrecan and collagen-II [174, 175]. The gene discussed is ADAMTS4; the disease is intervertebral disk degenerative disorder.