PMID- 11229466
OWN - NLM
STAT- MEDLINE
DCOM- 20010322
LR  - 20131121
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 44
IP  - 2
DP  - 2001 Feb
TI  - 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.
PG  - 351-60
AB  - 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.
FAU - Gouze, J N
AU  - Gouze JN
AD  - CNRS-Universite Henri Poincare-Nancy I, Vandoeuvre-les-Nancy, France.
FAU - Bordji, K
AU  - Bordji K
FAU - Gulberti, S
AU  - Gulberti S
FAU - Terlain, B
AU  - Terlain B
FAU - Netter, P
AU  - Netter P
FAU - Magdalou, J
AU  - Magdalou J
FAU - Fournel-Gigleux, S
AU  - Fournel-Gigleux S
FAU - Ouzzine, M
AU  - Ouzzine M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Interleukin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (glucosaminoglycans)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.4.1.135 (galactosylgalactoylxylosylprotein 3-beta-glucuronosyltransferase)
RN  - EC 2.4.1.17 (Glucuronosyltransferase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - N08U5BOQ1K (Glucosamine)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/metabolism
MH  - Dinoprostone/metabolism
MH  - Down-Regulation/drug effects
MH  - Glucosamine/pharmacology
MH  - Glucuronosyltransferase/*biosynthesis/genetics/*physiology
MH  - Glycosaminoglycans/*biosynthesis
MH  - Interleukin-1/*pharmacology
MH  - Male
MH  - Matrix Metalloproteinase 3/genetics
MH  - Nitric Oxide/biosynthesis
MH  - Osteoarthritis/drug therapy
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
EDAT- 2001/03/07 10:00
MHDA- 2001/03/27 10:01
CRDT- 2001/03/07 10:00
PHST- 2001/03/07 10:00 [pubmed]
PHST- 2001/03/27 10:01 [medline]
PHST- 2001/03/07 10:00 [entrez]
AID - 10.1002/1529-0131(200102)44:2<351::AID-ANR53>3.0.CO;2-M [doi]
PST - ppublish
SO  - Arthritis Rheum. 2001 Feb;44(2):351-60. doi: 
      10.1002/1529-0131(200102)44:2<351::AID-ANR53>3.0.CO;2-M.