Interleukin-1beta down-regulates the expression of glucuronosyltransferase I, a key enzyme priming glycosaminoglycan biosynthesis: influence of glucosamine on interleukin-1beta-mediated effects in rat chondrocytes

Arthritis Rheum. 2001 Feb;44(2):351-60. doi: 10.1002/1529-0131(200102)44:2<351::AID-ANR53>3.0.CO;2-M.


Objective: To assess the variations of galactose-beta-1,3-glucuronosyltransferase I (GlcAT-I) expression related to the decrease in proteoglycan synthesis mediated by interleukin-1beta (IL-1beta) in rat chondrocytes, and to evaluate the influence of glucosamine on the effects elicited by this proinflammatory cytokine.

Methods: Rat articular chondrocytes in primary monolayer cultures or encapsulated into alginate beads were treated with recombinant IL-1beta in the absence or presence (1.0-4.5 gm/liter) of glucosamine. Variations of GlcAT-I and expression of stromelysin 1 (matrix metalloproteinase 3 [MMP-3]) messenger RNA (mRNA) were evaluated by quantitative multistandard reverse transcriptase-polymerase chain reaction. In vitro enzymatic activity of GlcAT-I was measured by thin-layer chromatography, with radiolabeled UDP-glucuronic acid and a digalactoside derivative as substrates. Proteoglycan synthesis was determined by ex vivo incorporation of Na2-35SO4. Nitric oxide synthase and cyclooxygenase activities were monitored by the evaluation of nitrite (NO2-) and prostaglandin E2 (PGE2) produced in the culture medium, respectively.

Results: IL-1beta treatment resulted in a marked inhibition of GlcAT-I mRNA expression and in vitro catalytic activity, together with a decrease in proteoglycan synthesis. In addition, glucosamine was able to prevent, in a dose-dependent manner, the inhibitory effects of IL-1beta. In the same way, the amino sugar reduced NO2- and PGE2 production induced by IL-1beta. Finally, the up-regulation of stromelysin 1 (MMP-3) mRNA expression by IL-1beta was fully prevented by glucosamine.

Conclusion: The results of this study suggest that the deleterious effect of IL-1beta on the anabolism of proteoglycan could involve the repression of GlcAT-I, a key enzyme in the biosynthesis of glycosaminoglycan. Glucosamine was highly effective in preventing these IL-1beta-mediated suppressive effects. The amino sugar also prevented the production of inflammatory mediators induced by the cytokine. This action could account for a possible beneficial effect of glucosamine on osteoarthritic articular cartilage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Dinoprostone / metabolism
  • Down-Regulation / drug effects
  • Glucosamine / pharmacology
  • Glucuronosyltransferase / biosynthesis*
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / physiology*
  • Glycosaminoglycans / biosynthesis*
  • Interleukin-1 / pharmacology*
  • Male
  • Matrix Metalloproteinase 3 / genetics
  • Nitric Oxide / biosynthesis
  • Osteoarthritis / drug therapy
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar


  • Glycosaminoglycans
  • Interleukin-1
  • RNA, Messenger
  • glucosaminoglycans
  • Nitric Oxide
  • galactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferase
  • Glucuronosyltransferase
  • Matrix Metalloproteinase 3
  • Dinoprostone
  • Glucosamine