Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage

Objective: The prevalence of osteoarthritis (OAs) increases with age and co incides with the accumulation of advanced glycation endproducts (AGEs) in a rticular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine th e effects of accumulation of AGEs on the turnover of the extracellular matr ix of human articular cartilage. Design: Chondrocyte mediated cartilage degradation (GAG release, colorimetr ic) was measured in human articular cartilage of donors aged 19-82 years (N =30, 4-day culture). In addition, to mimic the age-related increase in AGE levels in vitro, cartilage was cultured in the absence or presence of gluco se, ribose or threose. Cartilage degradation and proteoglycan synthesis ((S O42-)-S-35 incorporation) were measured and related to the degree of cartil age AGE levels (fluorescence at 360/460 nm). Results: Chondrocyte-mediated degradation of articular cartilage (i.e. GAG release) decreased with increasing age of the cartilage donor (r= -0.43, P< 0.02). In vitro incubation of cartilage with glucose, ribose or threose res ulted in a range of AGE levels that was highly correlated to the chondrocyt e-mediated cartilage degradation (r=-0.77, P<0.001, N=26). In addition, in these in vitro glycated cartilage samples, a decrease in proteoglycan synth esis was observed at increasing AGE levels (r=-0.54, P<0.005, N=25). Conclusions: This study shows that an increase in AGE levels negatively aff ects the proteoglycan synthesis and degradation of articular cartilage. In combination, these two effects reduce the turnover of the cartilage and the reby the maintenance and repair capacity of the tissue. By this mechanism, the age-related increase in cartilage AGE levels may contribute to the deve lopment of OA. (C) 2001 OsteoArthritis Research Society International.