Quantitative biochemical changes in the human lumbar intervertebral disc

The intervertebral disc has been identified as a possible contributor to two very common back disorders: degenerative disc disease and scoliotic deformity. Little is known about the composition and turnover of extracellular matrix in the human intervertebral disc and end-plate with these two pathologies.We studied 121 intervertebral discs representing all age groups and degeneration grades. In addition, fifteen scoliotic discs and seventeen control discs were analyzed.Synthesis in intervertebral discs, end-plates, and scoliotic tissues were measured by immunoassay measuring the content of a putative aggrecan biosynthesis marker (846) and contents of types I and II procollagen markers (CPI & CPII). The percentage of denatured type II collagen was assessed by the presence of an epitope that is exposed with cleavage of type II collagen.We identified three matrix turnover phases in the intervertebral disc and end-plate. Phase I (growth) is characterized by active synthesis of matrix molecules and active denaturation of type II collagen. Phase II (maturation and ageing phase) is distinguished by progressive drops in synthetic activity and denaturation of type II collagen. Phase III (degeneration and fibrotic phase) is illustrated by decreased synthesis of aggrecan and type II procollagen and an increase in collagen type II denaturation and type I procollagen synthesis, the later dependent on age and grade of tissue degeneration.The results of the scoliotic study indicate that synthesis of type II procollagen in the end-plate and annulus was higher in scoliotic discs. Aggrecan synthesis showed a similar trend in the nucleus pulposus of scoliotic disc. By contrast, the contents of hydroxyproline, glycosaminoglycan, and water were significantly lower in scoliotic discs while total protein content was higher in scoliotic discs, indicating that non-collagenous protein content was increased in scoliotic discs. This elevated synthetic activity without an associated collagen denaturation reflects an overall synthetic response without an increased matrix turnover, suggesting that scoliotic changes are due to an altered and ineffective synthetic response to a pathologic mechanical environment.This thesis represents the first in situ quantitation of human lumbar intervertebral disc matrix composition and turnover with ageing, degeneration, and scoliotic change. These observations are an important advancement in our biochemical understanding of disc ageing, disc degeneration, and adolescent idiopathic scoliosis