Trellu, SabineCourties, AliceJaisson, StéphaneGorisse, LaëtitiaGillery, PhilippeKerdine-Römer, SaadiaVaamonde-García, CarlosHouard, XavierEkhirch, François-PaulSautet, AlainFriguet, BertrandJacques, ClaireBerenbaum, FrancisSellam, Jérémie2024-06-132024-06-132019-01-11Trellu S, Courties A, Jaisson S, Gorisse L, Gillery P, Kerdine-Römer S, Vaamonde-Garcia C, Houard X, Ekhirch FP, Sautet A, Friguet B, Jacques C, Berenbaum F, Sellam J. Impairment of glyoxalase-1, an advanced glycation end-product detoxifying enzyme, induced by inflammation in age-related osteoarthritis. Arthritis Res Ther. 2019 Jan 11;21(1):18.1478-6354http://hdl.handle.net/2183/36890[Abstract] Background: Accumulation 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. Methods: Ex 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. Results: Ex 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. Conclusion: Glo-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.engCreative Commons Attribution 4.0 International License (CC-BY 4.0)http://creativecommons.org/licenses/by/4.0/Advanced glycation end-productAgingCarboxymethyl-lysineChondrocyteGlyoxalaseOsteoarthritisjournal articleopen access10.1186/s13075-018-1801-y