Age Dependent Expression of Cartilage Proteoglycans

Cs-Szabo, Gabriella

Abstract

Morphological abnormalities (usually surface erosion) of the articular cartilage can be detected in approximately 70 percent of the human population over age 65. Essentially everyone with these degenerative abnormalities of the articular cartilage is listed under one of the most frequent age-associated disease, osteoarthritis (OA). Osteoarthritis, however, is a complex joint disease and, while it is characteristic, cartilage erosion is only one concomitant symptom of the disease process. We hypothesize that the degradation of articular cartilage is essentially an age-associated physiological process of heavily-used joints, and OA is the result of pathological events accompanies by change of chondrocyte phenotype. Now, we propose comparative studies of biochemical and histopathological parameters in an age-range of 40-70-year old population having no clinical records of joint abnormalities. To confirm our hypothesis, these results will be correlated with our previous observations of clinically diagnosed OA groups. We will measure four biochemical parameters (re-expression of a fetal-type epitope of aggrecan, substitution of fibromodulin with keratin sulfate, appearance of splice variants of decorin, and increased expression of small proteoglycans) which appear to be obligatory components of chondrocyte phenotype in OA, but not in normal aging cartilage. These normal versus altered chondrocyte phenotypes will then be correlated with the morphological appearance of the articular cartilage. We propose two specific aims: (1) to follow biochemical changes of cartilage components specifically altered in OA but not expected in normal aging tissue, and (2) to correlate these biochemical samples of patients with clinically end-stage OA. These experiments will explore molecular changes during the aging of cartilage and may segregate normal aging events from those of early OA changes.