Glucosamine modulates IL-1-induced activation of rat chondrocytes at a receptor level, and by inhibiting the NF-κB pathway

We recently reported that glucosamine reversed the decrease in proteoglycan synthesis and in UDP-glucuronosyl- transferase I mRNA expression induced by interleukin-1beta (IL-1beta) [Arthritis Rheum. 44 (2001) 351-360]. In the present work, we show that glucosamine does not exert the same effects when chondrocytes; were stimulated with reactive oxygen species (ROS). In order to better understand its mechanism of action, we determined if glucosamine could prevent the binding of IL-1beta to its cellular receptors or could interfere with its signaling pathway at a post-receptor level. Addition of glucosamine to rat chondrocytes treated with IL-1beta or with ROS decreased the activation of the nuclear factor kappaB, but not the activator protein-1. After treatment with IL-1beta, glucosamine increased the expression of mRNA encoding the type II IL-1beta receptor. These results emphasize the potential role of two regulating proteins of the IL-1beta signaling pathway that could account for the beneficial effect of glucosamine in osteoarthritis. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.