Delayed formation of proteoglycan aggregate structures in human articular cartilage disease states.

Proteoglycans are major components of many extracellular matrices. In cartilage, they provide reversible resistance to compression and exist as molecules with molecular weights (MWs) of 1-3 x 10(6). There is a central protein core of MWs approximately 2 x 10(5) (refs 1, 2) with specialized subregions, one containing mainly the chondroitin sulphate chains, another most of the keratan sulphate chains, and a third is a largely globular structure interacting specifically with both hyaluronic acid and a link protein to form stable aggregate structures such as those identified in human articular cartilage. In embryonic and tissue culture systems, proteoglycans are isolated as aggregate structures in as little as 5--10 min after synthesis (sulphation) with no nonaggregating precursor detected. However, Heinegärd and Hascall have characterized the small proportion of nonaggregating proteoglycan present in bovine nasal septum cartilage and found that it contained more peptide than the aggregating proteoglycan. Work by Upholt et al. has suggested that the MW of unprocessed protein core, synthesized by a wheat-germ translating system from chick sternal cartilage mRNA, is approximately 340,000, leaving open the possibility of intermediates. I report here the presence, in some human cartilages, of a proteoglycan population that initially will not aggregate with the hyaluronic acid but subsequently can be chased into aggregate.