title: Glucosamine sulfate reduces prostaglandin E(2) production in osteoarthritic chondrocytes through inhibition of microsomal PGE synthase-1.
abstract: OBJECTIVE
  Glucosamine sulfate (GS) has been inferred to have a potential antiinflammatory effect on osteoarthritis (OA). We investigated its effect on prostaglandin E(2) (PGE(2)) in human OA chondrocytes, and the level in the PGE(2) pathway at which its effect takes place.
  
  
  METHODS
  We investigated the effect of GS treatment (0.05, 0.2, 1.0, and 2.0 mM) in OA chondrocytes in the absence or presence of interleukin 1ß (IL-1ß; 100 pg/ml). We determined the expression levels and protein production/activity of PGE(2), cyclooxygenase-1 (COX-1), COX-2, microsomal PGE synthase-1 (mPGES-1), glutathione, and peroxisome proliferator-activated receptor-γ (PPARγ), using specific primers, antibodies, and assays.
  
  
  RESULTS
  GS treatment at 1 and 2 mM significantly inhibited (p ≤ 0.03) production of endogenous and IL-1ß-induced PGE(2). GS in both the absence and presence of IL-1ß did not significantly modulate COX-1 protein production, but GS at 1 and 2 mM demonstrated a decrease in COX-2 glycosylation in that it reduced the molecular mass of COX-2 synthesis. Under IL-1ß stimulation, GS significantly inhibited mPGES-1 messenger RNA expression and synthesis at 1 and 2 mM (p ≤ 0.02) as well as the activity of glutathione (p ≤ 0.05) at 2 mM. Finally, in both the absence and presence of IL-1ß, PPARγ was significantly induced by GS at 1 and 2 mM (p ≤ 0.03).
  
  
  CONCLUSIONS
  Our data document the potential mode of action of GS in reducing the catabolism of OA cartilage. GS inhibits PGE(2) synthesis through reduction in the activity of COX-2 and the production and activity of mPGES-1. These findings may, in part, explain the mechanisms by which this drug exerts its positive effect on OA pathophysiology.
authors.affiliation: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre, Notre-Dame Hospital, Montreal, Quebec H2L 4M1, Canada.
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.forename: François
authors.initials: F
authors.lastname: Mineau
authors.forename: Hassan
authors.initials: H
authors.lastname: Fahmi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Pelletier
authors.forename: Johanne
authors.initials: J
authors.lastname: Martel-Pelletier
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D005260:Female; D005944:Glucosamine / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D047495:PPAR gamma / Q000378:metabolism; D000071876:Prostaglandin-E Synthases
chemical_list: D053583:Interleukin-1beta; D047495:PPAR gamma; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases; D005978:Glutathione; D015232:Dinoprostone; D005944:Glucosamine