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

• approximately 100 chondroitin sulfate and 50 keratan sulfate chains are attached;

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

• The chondrocyte: a cell under pressure.
• Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes.
• Synthesis of chondrocytic keratan sulphate-containing proteoglycans by human chondrosarcoma cells in long-term cell culture.
• Ultrastructural modifications of proteoglycans coincident with mineralization in local regions of rat growth plate.
• Electron microscopic studies of cartilage proteoglycans: Direct evidence for the variable length of the chondroitin sulfate-rich region of proteoglycan subunit core protein.
• Assembly of newly synthesized proteoglycan and link protein into aggregates in cultures of chondrosarcoma chondrocytes.
• Specific inhibition of type I and type II collagen fibrillogenesis by the small proteoglycan of tendon.
• Expression of a Wide Range of Extracellular Matrix Molecules in the Tendon and Trochlea of the Human Superior Oblique Muscle