IDD is considered an age-related disease. After going through a degenerative cascade, it ultimately results in the loss of structural integrity, limited movement, pain, and decreased quality of life [10]. Causative factors of IDD can be categorized into passive destruction, including a violent blow or postural abrasion, and progressive changes. The latter is associated with aging and external environmental factors such as smoking, obesity, inflammation, and oxidation, etc. [47]. All of the above play a pathogenic role by changing the structure and metabolism of the IVD. A normal IVD is an avascular and innervated airtight fibrocartilaginous tissue located between the vertebrae. It consists of three parts: the nucleus pulposus (NP), the annulus fibrosus (AF), and the endplate (EP) [48]. Centrally located, the NP is surrounded by the AF, with the outermost EP wrapping the two structures together. Together, they constitute a closed cushioning system against stress, which enables the IVD to absorb and disperse loads from the vertebrae [10].When IDD occurs, one of the most striking changes is the ECM disorder caused by NP cell damage [49]. Collagens (mainly type I and II collagens), proteoglycans, and elastins comprise the main components of the ECM. Among them, aggrecan is the main proteoglycan found in IVDs and is a material basis of ECM homeostasis [50]. Matrix metalloproteinases (MMPs) [51], mainly including MMP1, 2, 3, 7, 8, 10, and 13, as well as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) [52], mainly including ADAMTS-1, 4, and 5, largely contribute to the degradation of the ingredients outlined above. The critical step of ECM disorder is proteoglycan degradation, accounting for the decreased hydration capacity of IVDs. This feature reduces the compression capacity and easily causes the expansion of the NP, resulting in cascading changes [53]. Divided into the outer, middle, and inner layers, the AF is a lamellar structure rich in collagens which can disperse mechanical stress to maintain the flexibility and stability of the spine. The nerve fibers and blood vessels distributed in the AF can transport nutrients to maintain the metabolism balance in the NP [54]. Apart from providing nutrients, the AF can disperse stress to prevent the radial disc bulge of the NP. At the same time, the additional stress caused by NP denaturation adds a burden to the outer layer of the AF. Specifically, the interval between the AF and the NP is vague, and the gaps between each layer are increased or even broken, eventually accelerating the loss of proteoglycan and type I collagen fibers [55]. The destruction of this structure leads to a functional change. In the AF, this is manifested by a decrease in antistretching ability and increased angiogenesis, triggering neuropathic pain and further impairing tissue homeostasis [56]. Likewise, the EP has the function of fixing and dispersing mechanical stress. In addition, the EP also performs as a translucent barrier between the avascular IVD and highly vascularized vertebrae, transporting oxygen, glucose, and metabolites through diffusive movement [57]. During the IDD process, EP becomes thinner and more calcified [58], resulting in a vicious circle as a result of hindered solute diffusion. Eventually, inflammation, hypoxia, acidity, and nutrient deprivation can be witnessed in the microenvironment of IDD. Biochemical and pathological changes, as noted above, aggravate the loss of proteoglycans, inhibit collagen cross-linking, and form osteophytes [59]. T1-weighted images show the diagnostic indicator of hyperintensity on the torn AF, whereas T2-weighted images display low signals of atrophy and dehydration in the NP region [60].