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 1β (IL-1β 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-1β-induced PGE 2. GS in both the absence and presence of IL-1β 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-1β, PPARγ was significantly induced by GS at 1 and 2 mM (p ≤0.03). Conclusion. 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. The Journal of Rheumatology Copyright © 2012. All rights reserved.