Hyaluronate degradation as an alternative mechanism for proteoglycan release from cartilage during interleukin-1beta-stimulated catabolism

Biochem J. 2002 Mar 1;362(Pt 2):473-9. doi: 10.1042/0264-6021:3620473.


Data presented previously suggest that release of components of the cartilage matrix, in response to catabolic agents, cannot be accounted for by proteolytic mechanisms alone. In the present study, the release of glycosaminoglycan-containing components from bovine nasal cartilage cultured in the presence of interleukin-1beta, and from bovine nasal, fetal bovine epiphyseal and adult human articular cartilage cultured in the presence of retinoic acid, was accompanied by the loss of link protein and hyaluronate into the culture medium. Chromatographic analysis of the released hyaluronate showed it to be markedly reduced in size relative to that extracted from the corresponding tissue. It is proposed that, under stimulation by catabolic agents, two independent, but concurrent, mechanisms act to promote the release of aggrecan from the cartilage matrix. First, proteolytic cleavage of the aggrecan core protein results in the production of glycosaminoglycan-containing fragments that are free to diffuse from the tissue. Secondly, cleavage of hyaluronate renders portions of the proteoglycan aggregate small enough so that complexes of aggrecan (or fragments containing its G1 domain) and link protein are released from the tissue. It is likely that both mechanisms contribute to cartilage metabolism in normal physiology and pathology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage / drug effects
  • Cartilage / metabolism*
  • Cattle
  • Chromatography, Gel
  • Extracellular Matrix Proteins / metabolism
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / isolation & purification
  • Hyaluronic Acid / metabolism*
  • Interleukin-1 / pharmacology*
  • Kinetics
  • Nasal Septum / drug effects
  • Nasal Septum / metabolism*
  • Organ Culture Techniques
  • Proteins / metabolism
  • Proteoglycans / isolation & purification
  • Proteoglycans / metabolism*


  • Extracellular Matrix Proteins
  • Interleukin-1
  • Proteins
  • Proteoglycans
  • link protein
  • Hyaluronic Acid