The human lumbar intervertebral disc: evidence for changes in the biosynthesis and denaturation of the extracellular matrix with growth, maturation, ageing, and degeneration.

Abstract

Very little is known about the turnover of extracellular matrix in the human intervertebral disc. We measured concentrations of specific molecules reflecting matrix synthesis and degradation in predetermined regions of 121 human lumbar intervertebral discs and correlated them with ageing and Thompson grade of degeneration.Synthesis in intervertebral discs, measured by immunoassay of the content of a putative aggrecan biosynthesis marker (846) and the content of types I and II procollagen markers, is highest in the neonatal and 2-5-yr age groups. The contents of these epitopes/molecules progressively diminished with increasing age. However, in the oldest age group (60-80 yr) and in highly degenerated discs, the type I procollagen epitope level increased significantly.The percentage of denatured type II collagen, assessed by the presence of an epitope that is exposed with cleavage of type II collagen, increased twofold from the neonatal discs to the young 2-5-yr age group. Thereafter, the percentage progressively decreased with increasing 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 molecules and active denaturation of type II collagen. Phase II (maturation and ageing) is distinguished by a progressive drop in synthetic activity 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 procollagen synthesis, both dependent on age and grade of tissue degeneration. ( J. Clin. Invest. 1996. 98:996-1003.)

Ageing and degenerative changes of the intervertebral disc and their impact on spinal flexibility

“…Within the nucleus pulposus, the water content was found to decrease from 5.8 gH 2 O/g dry weight at an age of 14 years (85 % volume fraction) to 3.3 gH 2 O/g dry weight at age 91 years (75 %) [66]. For the NP, primarily, a loss of proteoglycans was observed [7,34]. For the AF, a change in water content, although to a more limited extent in comparison with the NP, as well as collagen content is observed during ageing [7].…”

“…For the NP, primarily, a loss of proteoglycans was observed [7,34]. For the AF, a change in water content, although to a more limited extent in comparison with the NP, as well as collagen content is observed during ageing [7]. The decrease in the proteoglycan content is linked to a reduction of the swelling pressure, for which values ranging from 0.19 MPa (age of 37 years) to 0.05 MPa (age of 91 years) were measured [66].…”

Tissue elasticity and the ageing elastic fibre

“…Aspartic acid racemization (AAR) studies estimate that the half-lives of types I and II collagen in human skin, articular cartilage and intervertebral disc are 15, 95 and 117 years, respectively (Sivan et al 2008;Verzijl et al 2000). The lower turnover rates and hence longer half-lives of cartilage collagens compared with dermal collagens may be a consequence of the lower cell densities and hence lower catabolic and anabolic rates which prevail in mature cartilage (Antoniou et al 1996). The stability of the tissue collagens is matched and in many cases exceeded by the longevity of elastic fibres and their molecular components.…”

The vertebral endplate: disc degeneration, disc regeneration

“…The biochemical composition of the endplates, from normality through the spectrum of degenerative conditions, has been documented extensively [4,6]. Of the several species of collagen present in the disc Type X is thought to be the most important in the endplate since it is a marker of hypertrophic chondrocytes and is involved with calcification [1].…”