This meta-analysis shows great heterogeneity. Hyaluronic acid may be useful to increase functional capacity and corticosteroids to decrease pain in thumb osteoarthritis at week 24.
BackgroundAccumulation of advanced glycation end-products (AGEs) is involved in age-related osteoarthritis (OA). Glyoxalase (Glo)-1 is the main enzyme involved in the removal of AGE precursors, especially carboxymethyl-lysine (CML). We aimed to investigate the expression of several AGEs and Glo-1 in human OA cartilage and to study chondrocytic Glo-1 regulation by inflammation, mediated by interleukin (IL)-1β.MethodsEx vivo, we quantified AGEs (pentosidine, CML, methylglyoxal-hydroimidazolone-1) in knee cartilage from 30 OA patients. Explants were also incubated with and without IL-1β, and we assessed Glo-1 protein expression and enzymatic activity. In vitro, primary cultured murine chondrocytes were stimulated with increasing concentrations of IL-1β to assess Glo-1 enzymatic activity and expression. To investigate the role of oxidative stress in the IL-1β effect, cells were also treated with inhibitors of mitochondrial oxidative stress or nitric oxide synthase.ResultsEx vivo, only the human cartilage CML content was correlated with patient age (r = 0.78, p = 0.0031). No statistically significant correlation was found between Glo-1 protein expression and enzymatic activity in human cartilage and patient age. We observed that cartilage explant stimulation with IL-1β decreased Glo-1 protein expression and enzymatic activity. In vitro, we observed a dose-dependent decrease in Glo-1 mRNA, protein quantity, and enzymatic activity in response to IL-1β in murine chondrocytes. Inhibitors of oxidative stress blunted this downregulation.ConclusionGlo-1 is impaired by inflammation mediated by IL-1β in chondrocytes through oxidative stress pathways and may explain age-dependent accumulation of the AGE CML in OA cartilage.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1801-y) contains supplementary material, which is available to authorized users.
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