THE HUMAN LUMBAR INTERVERTEBRAL DISC - EVIDENCE FOR CHANGES IN THE BIOSYNTHESIS AND DENATURATION OF THE EXTRACELLULAR-MATRIX WITH GROWTH, MATURATION, AGING, AND DEGENERATION

Very little is known about the turnover of extracellular matrix in the human intervertebral disc, We measured concentrations of specific mol ecules reflecting matrix synthesis and degradation in predetermined re gions of 121 human lumbar intervertebral discs and correlated them wit h ageing and Thompson grade of degeneration, Synthesis in intervertebr al discs, measured by immunoassay of the content of a putative aggreca n biosynthesis marker (846) and the content of types I and II procolla gen markers, is highest in the neonatal and 2-5-yr age groups. The con tents of these epitopes/molecules progressively diminished with increa sing age. However, in the oldest age group (60-80 yr) and in highly de generated discs, the type I procollagen epitope level increased signif icantly. The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II colla gen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increa sing age; however, it increased significantly in the oldest group and in highly degenerate discs, We identified three matrix turnover phases , Phase I (growth) is characterized by active synthesis of matrix mole cules and active denaturation of type II collagen, Phase Ii (maturatio n and ageing) is distinguished by a progressive drop in synthetic acti vity and a progressive reduction in denaturation of type II collagen, Phase III (degeneration and fibrotic) is illustrated by evidence for a lack of increased synthesis of aggrecan and type II procollagen, but also by an increase in collagen type II denaturation and type I procol lagen synthesis, both dependent on age and grade of tissue degeneratio n.