The human lumbar endplate - Evidence of changes in biosynthesis and denaturation of the extracellular matrix with growth, maturation, aging, and degeneration

Study Design. The authors measured concentrations of specific molecules reflecting matrix synthesis and degradation in 121 human endplates and correlated them with aging and grade of degeneration. Objectives. Abnormal endplate development has been implicated in many spinal abnormalities, yet little is known about endplate matrix component turnover. Summary of Background Data. Techniques are available to perform an in situ investigation of matrix component turnover with aging and degeneration. Methods. Newly synthesized aggrecan and Type I and Type II procollagens were measured with recently developed immunoassays. Percentage of denatured Type II collagen was assessed with a new enzyme-linked immunosorbent inhibition assay. Results. Synthesis in endplates, measured by content of an aggrecan marker (846) and content of Types I and II procollagen markers (CPI and CPII), is highest in the neonatal and 2- to 5-year age groups and steadily diminishes with increasing age. However, in the oldest age group and in highly degenerated discs, the CPI epitope level increased significantly. Percentage of denatured Type II collagen, assessed by the presence of an epitope exposed with the cleavage of Type II collagen, increased from the neonatal to the 2- to 5-year age groups. The percentage progressively decreased with increasing age. However, it significantly increased in endplates from highly degenerated discs. Conclusions. The authors identified three matrix turnover phases, related to age and grade of degeneration. Phase I (growth) is characterized by active synthsis of matrix molecules and active denaturation of Type II collagen. Phase II (aging and maturation) is distinguished by a drop in synthetic activity and a reduction In denaturation of Type II collagen. Phase III (degenerative) is illustrated by an increase in Type II collagen denaturation and Type I procollagen synthesis, both related to grade of tissue degeneration.