Abstract

Introduction: Oxidative stress is an important component of the pathogenesis of osteoarthritis. NADPH oxidase Nox4 is a reactive oxygen species (ROS) producing enzyme highly expressed in chondrocytes and may be a key contributor of this oxidative component by regulating Matrix metalloproteases (MMPs) expression. In order to optimize the Glucosamine sulphate (GS) efficacy against osteoarthritis, a new therapeutic association (Glucosamine Copper Ginger) has been developed (GSCG). In this study, we compared the effects of GSCG and GS on Nox4 activity, MMPs expression in IL-1β-stimulated C-20/A4 chondrocytes. Methods: C-20/A4 chondrocytes were pre-treated with GSCG or GS. After IL-1β stimulation, we assessed MMPs expression by Western blot or apoptosis using the activation of caspase 3 as marker. Impact of compounds on Nox4 activity was measured by chemiluminescence on the inducible Nox4 expressing cells line HEK293 T-REx™. Results: ROS production and related MMP1 expression were significantly decreased (respectively by 30% and 40%) after pre-incubation with GSCG. On the other hand, no significant effect was observed after GS treatment. ADAMTS5 expression was markedly decreased by GS and GSCG. Moreover, results reported a significant decrease in the IL-1β-induced caspase 3 activation in presence of GS and GSCG. Conclusions: This study provided experimental evidence that glucosamine sulfate decreases ADAMTS5 expression and apoptosis. In addition, ginger root and copper sulphate decreased pro-MMP1 expression by regulating NOX4 activity. Our data suggest the implication of Heme Oxygenase-1 in the molecular mechanisms. These findings emphasize in vitro the potential beneficial effects of therapeutic association of Glucosamine, copper sulphate and Ginger extract.

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