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

Abstract

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 × 10⁶. There is a central protein core of MWs approximately 2 × 10⁵ (refs 1, 2) with specialized subrogions, one containing mainly the chondroitin sulphate chains³, another most of the keratan sulphate chains⁴, and a third is a largely globular structure interacting specifically with both hyaluronic acid⁵ and a link protein⁶ to form stable aggregate structures such as those identified in human articular cartilage⁷. In embryonic⁸ and tissue culture systems⁹, proteoglycans are isolated as aggregate structures in as little as 5–10 min after synthesis (sulphation) with no nonaggregating precursor detected. However, Heinegård 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 proteoglycan¹⁰. Work by Upholt et al.¹¹ has suggested that the MW of unprocessed protein core, synthesized by a wheat-germ translating system from chick sternal cartilage mRNA, is ∼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.