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Proteoglycans in Cartilage

(see also: cartilage topics)

Discussion

  • proteoglycan is a macromolecule constructed of a protein core to which many glycosaminoglycan chains are attached - protein with bound side chains (glycosaminoglycans);
    • to this proteoglycan aggregate, hyaluronic acid is non covalently bound;
    • in osteoarthritis, there is a characteristic reduction in a aggregrating proteoglycans;
  • about 10% of wt of proteoglycan molecule is protein, and 90% is glycosaminoglycans;
  • proteoglycans carry fixed negative charges and attract a high concentration of cations;
  • glycans: negatively chondroitin & keratan sulfate repel each other, so that glycosaminoglycan electrostaticrepulsion along chain and between chains and therefore chains assume a fully extended conformation;

sub-types

  • aggrecans (large agregating proteoglycans)
    • key proteoglycan molecule in the cartilage matrix and creates the osmotic properties necessary for cartilage to resist compressive loads;
  • small proteoglycans (decorin (coats the outside of the collagen fibrils), biglycan, and fibromodulin);

link protein

  • small glycoprotein serves to stabilize non-covalent association of the proteoglycan subunits with hyaluronic acid in aggregate;

protein core

aggrecan

  • major proteoglycan in cartilage, linked to hyaluronan;
  • provides unique capacity to bear load and resist compression
  • hydrated and thereby allows cartilage to resist a compressive load
  • loss of aggrecan is the primary event leading to the destruction of cartilage;
  • aggrecanases: enzymes which degrate aggrencans;
    • ADAMTS (a disintegrin and metalloproteinase) family of proteinases
    • aggrecanase-1 and aggrecanase-2

References