ACAN and intervertebral disk degenerative disorder: During the development of IDD, multiple abnormal stimuli can increase the level of inflammatory cytokines—especially interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α)—which then promote the degradation of aggrecan and collagen, the generation of catabolic factors [e.g., matrix metalloproteinases (MMPs)], the leakage of NP cells, and changes to the phenotypes of the intervertebral disk cells (Risbud and Shapiro, 2014; Xu et al., 2017; Cheng et al., 2018).