Age-related decrease in proteoglycan synthesis of human articular chondrocytes - The role of nonenzymatic glycation

Objective. To examine the effect of nonenzymatic glycation of cartilage ext racellular matrix on the synthetic activity of chondrocytes. Methods. The proteoglycan-synthesis rate ((SO42-)-S-35 incorporation) and l evels of advanced nonenzymatic glycation (determined by high-performance li quid chromatography measurement of pentosidine) were evaluated in human art icular cartilage from 129 donors, varying in age from 25 to 88 years, and i n cartilage,with enhanced levels of advanced glycation end-products (AGEs) resulting from incubation with ribose. Results. Cartilage showed a strong age-related increase in pentosidine leve ls (r = 0.97, P < 0.0005) and, concomitantly, a decrease in proteoglycan sy nthesis (r = -0.98, P < 0.0002). This decrease in proteoglycan synthesis co rrelated with the increase in pentosidine (r = -0.95, P < 0.02), Moreover, the elevation of pentosidine levels in the in vitro-ribosylated cartilage w as proportional with the decrease in proteoglycan synthesis (r = -0.95, P < 0.005). Conclusion. In both aged and in vitro AGE- enriched cartilage, the rate of proteoglycan synthesis was negatively correlated with the degree of glycati on. This suggests that the age-related increase in cartilage AGE levels may be responsible, at least in part, for the age-related decline in the synth etic capacity of cartilage.