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Impairment of glyoxalase-1, an advanced glycation end-product detoxifying enzyme, induced by inflammation in age-related osteoarthritis

  • Trellu, Sabine1, 2, 3, 4
  • Courties, Alice1, 2, 3, 4
  • Jaisson, Stéphane5
  • Gorisse, Laëtitia5
  • Gillery, Philippe5
  • Kerdine-Römer, Saadia6
  • Vaamonde-Garcia, Carlos1, 2, 3, 7
  • Houard, Xavier1, 2, 3
  • Ekhirch, François-Paul8
  • Sautet, Alain1, 9
  • Friguet, Bertrand1, 10
  • Jacques, Claire1, 2, 3
  • Berenbaum, Francis1, 2, 3, 4
  • Sellam, Jérémie1, 2, 3, 4
  • 1 Sorbonne University, UPMC Univ Paris 06, Paris, France , Paris (France)
  • 2 INSERM UMRS_938, CRSA, Paris, France , Paris (France)
  • 3 Inflammation-Immunopathology-Biotherapy Department (DHU i2B), Paris, France , Paris (France)
  • 4 Saint-Antoine Hospital, Department of Rheumatology, Assistance Publique - Hôpitaux de Paris (AP-HP), 184 rue du Faubourg Saint-Antoine, Paris, 75012, France , Paris (France)
  • 5 UMR MEDyC CNRS/URCA 7369, University of Reims Champagne-Ardenne, Reims, France , Reims (France)
  • 6 INSERM UMR 996, Univ Paris-Sud, University Paris-Saclay, Châtenay-Malabry, France , Châtenay-Malabry (France)
  • 7 University of A Coruña, Department of Physiotherapy, Cell Therapy and Regenerative Medicine Group, Medicine and Biological Science. Faculty of Health Sciences, A Coruña, 15006, Spain , A Coruña (Spain)
  • 8 Groupe Maussins, Clinique des Maussins-Ramsay, Générale de Santé, Paris, France , Paris (France)
  • 9 AP-HP, Saint-Antoine Hospital, Department of Orthopedic Surgery, Paris, France , Paris (France)
  • 10 UMR 8256 - IBPS, CNRS UMR 8256, INSERM U1164, Paris, F-75005, France , Paris (France)
Published Article
Arthritis Research & Therapy
BioMed Central
Publication Date
Jan 11, 2019
DOI: 10.1186/s13075-018-1801-y
Springer Nature


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.

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