Inhibition of glycosaminoglycan incorporation influences collagen network formation during cartilage matrix production

Biochem Biophys Res Commun. 2009 Feb 6;379(2):222-6. doi: 10.1016/j.bbrc.2008.12.028. Epub 2008 Dec 25.

Abstract

To understand cartilage degenerative diseases and improve repair procedures, we investigate the influence of glycosaminoglycans (GAGs) on cartilage matrix biochemistry and functionality. Bovine articular chondrocytes were cultured in alginate beads with(out) para-nitrophenyl-beta-d-xyloside (PNPX) to inhibit GAG incorporation into newly formed proteoglycans. As expected, GAG deposition in alginate beads decreased with increasing PNPX concentration. Next to GAGs, collagen deposition and cross-linking also decreased. In the presence of PNPX, GAGs and collagen were deposited further away from the chondrocyte than in the control and increased amounts were found in the culture medium. These changes resulted in decreased functional properties of the construct. We conclude that in our culture system, intact proteoglycans play a role in deposition of collagen and thus the formation of a functional matrix. The effect of less proteoglycans on the collagen network could explain why cartilage repair is ineffective in osteoarthritis and help us with development of new therapies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Cartilage / drug effects
  • Cartilage / growth & development*
  • Cartilage / metabolism
  • Cartilage / ultrastructure*
  • Cattle
  • Chondrocytes / cytology
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Collagen / metabolism
  • Collagen / ultrastructure*
  • Collagen Type II / genetics
  • Gene Expression
  • Glucuronic Acid / chemistry
  • Glycosaminoglycans / metabolism*
  • Glycosides / chemistry
  • Glycosides / pharmacology
  • Hexuronic Acids / chemistry
  • SOX9 Transcription Factor / genetics
  • Tissue Culture Techniques

Substances

  • Alginates
  • Collagen Type II
  • Glycosaminoglycans
  • Glycosides
  • Hexuronic Acids
  • SOX9 Transcription Factor
  • 4-nitrophenyl beta-D-xyloside
  • Glucuronic Acid
  • Collagen