AGGRECAN TURNOVER IN HUMAN ARTICULAR-CARTILAGE - USE OF ASPARTIC-ACIDRACEMIZATION AS A MARKER OF MOLECULAR AGE

Aggrecan is a key component of the cartilage matrix, During aging, man y changes occur in its composition and structure; in particular, there is an increase in the proportion of lower molecular weight monomers a nd of the ''free'' binding region. An important question has been whet her these changes represent alterations in biosynthesis or whether the y are due to the accumulation with age of the partially degraded fragm ents of the originally synthesized large monomer. In the present work we have used an independent tool, viz., the extent of racemization of aspartic acid to study the molecular ''age'' of different buoyant dens ity fractions of the aggrecan of human articular cartilage, as well as of isolated free binding region and link protein. By measuring the D/ L-Asp, ratio of the different aggrecan species, we were able to establ ish directly the relative residence times of these molecules in the ca rtilage matrix and, in combination with compositional and structural a nalyses, to define their ''history'' and calculate some of the kinetic s constants characterizing their turnover. The value of the turnover c onstant for the large monomer in fraction A1D1 is 0.206 per year, whic h corresponds to a half-life of 3.4 years, while the turnover constant for the free binding region is 0.027 per year, which corresponds to a half-life of 25 years. It is thus clear that the rate of formation an d turnover of the large monomer is much more rapid than the final degr adation of the free binding region fragments, which explains the accum ulation of the latter in cartilage during aging. (C) 1998 Academic Pre ss.