What is Intervertebral Disc Degeneration, and What Causes It?

Michael A. Adams, PhD; Peter J. Roughley, PhD


Spine. 2006;31(18):2151-2161. 

In This Article

Disc Metabolism

Cells in the anulus are elongated parallel to the collagen fibers, rather like fibroblasts. Cells in the nucleus are initially notochordal but are gradually replaced during childhood by rounded cells resembling the chondrocytes of articular cartilage. Anulus cells synthesize mostly collagen type I in response to deformation, whereas nucleus cells respond to hydrostatic pressure by synthesizing mostly proteoglycans and fine collagen type II fibrils. Cell density declines during growth,[7] and in the adult is extremely low, especially in the nucleus. Disc cell biology has been reviewed recently.[8,9]

In adult discs, blood vessels are normally restricted to the outmost layers of the anulus. Metabolite transport is by diffusion, which is important for small molecules, and by bulk fluid flow, which is important for large molecules.[8,10] Transport routes are shown in Figure 4. Low oxygen tension in the center of a disc leads to anaerobic metabolism, resulting in a high concentration of lactic acid and low pH.[8] In vitro experiments show that a chronic lack of oxygen causes nucleus cells to become quiescent, whereas a chronic lack of glucose can kill them.[12] Deficiencies in metabolite transport appear to limit both the density and metabolic activity of disc cells.[8] As a result, discs have only a limited ability to recover from any metabolic or mechanical injury. Endplate permeability and, therefore, disc metabolite transport normally decrease during growth and aging, and yet increase in the presence of disc degeneration and following endplate damage.[13] This is one essential difference between aging and degeneration.

Organization of the vertebral endplate. The vertebral endplate consists of hyaline cartilage weakly bonded to the perforated cortical bone of the vertebral body, and collagen fibers of the anulus and nucleus. Arrows indicate routes for nutrient transport from surrounding blood vessels into the central regions of the disc. Adapted from J Orthop Res 1993;11:747-57.[11]

Disc cells synthesize their matrix and break down existing matrix by producing and activating degradative enzymes, including matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase (ADAMS).[14,15,16,17,18,19,20] Molecular markers of matrix turnover are naturally most plentiful during growth but usually decline thereafter.[21] The major structural changes to the disc occur during fetal and juvenile growth, when the nucleus changes in consistency from a translucent fluid to a soft amorphous tissue,[22] caused mainly by an increase in collagen content. The proteoglycan content of the disc is maximal in the young adult and declines thereafter,[21] presumably because of proteolysis. Disc cells appear to adapt the properties of their matrix to suit prevailing mechanical demands, although the low cell density and lack of a blood supply ensure that changes are not as rapid or pronounced as in adjacent vertebrae.[23] Adaptive remodeling probably contributes to the large variation in compressive strength of adult discs, which ranges from 2.8 to 13.0 kN when they are tested in a manner that causes failure in the disc rather than the adjacent vertebra.[24]

Injured discs show increased levels of catabolic cytokines, increased MMP activity,[21,25] and scar formation,[26] especially in the vicinity of anular tears.[26,27] They also show evidence of renewed matrix turnover[21,28] and a more variable range of collagen fibril diameters.[29] However, gross injuries to a disc never fully heal. Scalpel cuts in the outer anulus fill with granulation tissue, with only the outer few millimeters being bridged by scar tissue.[30,31] Anular tears are not remodeled as in bone, presumably because the sparse cell population is unable to break down the large collagen fiber bundles of the anulus and replace them with new.[32] Collagen turnover time in articular cartilage is approximately 100 years[33] and could be even longer in the disc. Proteoglycan turnover is faster, possibly 20 years,[32] and some regeneration of nucleus pulposus is possible in young animals.[34] Injuries that affect the inner anulus or endplate decompress the nucleus,[35] and healing processes are then overtaken by severe degenerative changes.[31]


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