Skip to Main content Skip to Navigation
Journal articles

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

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.
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01980125
Contributor : Gestionnaire Hal-Su <>
Submitted on : Monday, January 14, 2019 - 11:06:05 AM
Last modification on : Wednesday, September 16, 2020 - 5:51:31 PM

File

Trellu2019_Article_ImpairmentO...
Publication funded by an institution

Identifiers

Citation

Sabine Trellu, Alice Courties, Stéphane Jaisson, Laëtitia Gorisse, Philippe Gillery, et al.. Impairment of glyoxalase-1, an advanced glycation end-product detoxifying enzyme, induced by inflammation in age-related osteoarthritis. Arthritis Research and Therapy, BioMed Central, 2019, 21, pp.18. ⟨10.1186/s13075-018-1801-y⟩. ⟨hal-01980125⟩

Share

Metrics

Record views

240

Files downloads

270