Molecular Biology of Degenerative Disc Disease

The intervertebral disc is a sophisticated anatomical structure composed predominantly of fibrocytes and chondrocytes embedded within an avascular extracellular matrix built from collagen fibers and proteoglycans. Intervertebral disc degeneration (IDD) is a long-standing and complex disorder that has been closely associated with the occurrence of low back pain, although the precise mechanisms driving the disease are still being worked out. The pathology is widely accepted as multifactorial, emerging from a combination of intrinsic factors and external influences—these include the ageing process, hereditary susceptibility, the nutritional environment of the disc, repetitive or excessive mechanical stress, metabolic disturbances and toxic exposures, and the possibility of low-virulence bacterial colonization. The degenerative cascade in the disc produces parallel changes in both architecture and biochemistry. From a structural standpoint, the affected disc loses water content, develops fissures and tears, and shows disorganization across the nucleus pulposus, annulus fibrosus, and adjacent endplates. On the biochemical front, the principal hallmarks include compromised solute diffusion, a fall in viable cell numbers, suppressed proteoglycan production, and a reorganization of the collagen network. The exact role played by inflammatory signaling molecules in driving these events, and whether growth factors can realistically be used to halt or reverse the cascade, are areas that still demand further clarification. Deepening our grasp of the molecular events behind disc degeneration is therefore central to designing the next generation of restorative and reparative interventions. Such strategies may seek to drive endogenous regeneration of the disc or to supply a biologically engineered substitute for the worn-out tissue, both of which could ultimately help patients living with this disabling problem. The present chapter examines, in sequence, the normal architecture of the IVD, the various contributory factors that drive IDD, the underlying molecular pathology of IDD, and its clinical relevance.