Intervertebral disc degeneration: biological and biomechanical factors

cluding cytokines, growth factors, enzymes, and enzyme inhibitors, in a paracrine or/and autocrine fashion.1,2 Anabolic regulators include polypeptide growth factors, such as insulin-like growth factor (IGF), transforming growth factor-β (TGF-β), and the bone morphogenetic proteins (BMPs).1–4 Other small molecules, such as the synthetic peptide of link protein, have also been reported to be regulators of matrix synthesis.5 The catabolic process is mediated by various enzymes, such as the matrix metalloproteinases (MMPs),6–16 members of a disintegrin-like and metalloprotease with thrombospondin motifs (ADAMTS) family (aggrecanases),17–19 and cytokines.13,20–26 Disc degeneration can result from an imbalance between the anabolic and catabolic processes or the loss of steadystate metabolism that is maintained in the normal disc. With IVD degeneration, the gradual loss of large PGs, such as aggrecan and versican, from the NP has been reported; however, in the AF, there is an initial upregulation of these proteins in the early stages of disc degeneration, followed by a downregulation in the late stage of disc degeneration.27 Therefore, therapeutic strategies might be different depending on the stage of disc degeneration and for the NP versus the AF. Therapeutic strategies for disc degeneration include an upregulation of important matrix proteins, such as aggrecan, or downregulation of proinflammatory cytokines and matrix-degrading enzymes, such as the MMPs and ADAMTSs, possibly by applying both strategies. The importance of nutrition to the IVD, which is the largest avascular tissue in the body, in the pathogenesis of disc disease is well recognized.28–36 To maintain the steady-state metabolism of the cells, the IVD requires proper nutrition, mainly by diffusion from the vertebral bodies and endplates.29 Trauma, cigarette smoking, deposition of calcium crystal, and other factors that disrupt the integrity of the endplates may affect diffusion and disturb the nutrition of the disc cells.28 It is important to assess the nutritional status of the degenerated Introduction