Nonenzymatic glycation of cartilage proteoglycans: an in vivo and in vitro study.

In this study we have investigated whether proteoglycans (aggrecan) are modified by nonenzymatic glycation as in collagen. Purified human aggrecan from osteoarthritic and normal human knee articular cartilage was assayed for pentosidine, a cross-link formed by nonenzymatic glycation, using reverse-phase HPLC. In addition, an in vitro study was done by incubation of purified bovine nasal cartilage aggrecan with ribose. Pentosidine was found in all the purified human aggrecan samples. 2-3% of the total articular cartilage pentosidine was found in aggrecan. Purified link protein also contained penosidine. The in vitro study led to pentosidine formation, but did not appear to increase the molecular size of the aggrecan suggesting that pentosidine was creating intramolecular cross-links. Similar amounts of glycation were found in osteoarthritic and normal cartilage. Like collagen, aggrecan and link proteins are crosslinked by nonenzymatic glycation in normal and osteoarthritic cartilage. Crosslinking could be reproduced, in vitro, by incubating aggrecan with ribose.