AGE-RELATED-CHANGES IN CARTILAGE PROTEOGLYCANS - QUANTITATIVE ELECTRON-MICROSCOPIC STUDIES

Biochemical and biophysical studies have shown that the composition an d sedimentation velocity of cartilage proteoglycans change with age, b ut these investigations cannot demonstrate the alterations in molecula r structure responsible for these changes. Development of quantitative electron microscopic methods has made it possible to define the age-r elated structural changes in aggregating proteoglycans and to correlat e the alterations in their structure with changes in tissue compositio n and morphology. Electron microscopic measurement of human and animal hyaline cartilage proteoglycans has shown that with increasing age th e length of the chondroitin sulfate-rich region of aggregating proteog lycan monomers (aggrecan molecules) decreases, the variability in aggr ecan length increases, the density of aggrecan keratan sulfate chains increases, the number of monomers per aggregate decreases, and the pro portion of monomers that aggregate declines. Proteoglycans from the nu cleus pulposus of the intervertebral disc show similar but more dramat ic age-related alterations. At birth, nucleus pulposus aggrecan molecu les are smaller and more variable in length than those found in articu lar cartilage. Within the first year of human life, the populations of aggregates and large aggrecan molecules analogous to those found in a rticular cartilage decline until few if any of these molecules remain in the central disc tissues of skeletally mature individuals. The mech anisms of the age-related changes in cartilage proteoglycans have not been fully explained, but measurement of proteoglycans synthesized by chondrocytes of different ages suggests that alterations in synthesis produce at least some of the age-related changes in aggrecan molecules . Degradation of aggrecan chondroitin sulfate-rich regions in the matr ix probably also contributes to the structural changes seen by electro n microscopy. Age-related changes in proteoglycan aggregation may be d ue to alterations in link protein function or inhibition of aggregatio n of newly synthesized aggrecan molecules by accumulation of degraded aggrecan molecules. (C) 1994 Wiley-Liss, Inc.