The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes–associated osteoarthritis
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The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes–associated osteoarthritisAutor(es)
Data
2017-07-06Cita bibliográfica
Vaamonde-Garcia C, Courties A, Pigenet A, Laiguillon MC, Sautet A, Houard X, Kerdine-Römer S, Meijide R, Berenbaum F, Sellam J. The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis. J Biol Chem. 2017 Sep 1;292(35):14505-14515.
Resumo
[Asbtract] Epidemiological findings support the hypothesis that type 2 diabetes mellitus (T2DM) is a risk factor for osteoarthritis (OA). Moreover, OA cartilage from patients with T2DM exhibits a greater response to inflammatory stress, but the molecular mechanism is unclear. To investigate whether the antioxidant defense system participates in this response, we examined here the expression of nuclear factor-erythroid 2-related factor (Nrf-2), a master antioxidant transcription factor, and of heme oxygenase-1 (HO-1), one of its main target genes, in OA cartilage from T2DM and non-T2DM patients as well as in murine chondrocytes exposed to high glucose (HG). Ex vivo experiments indicated that Nrf-2 and HO-1 expression is reduced in T2DM versus non-T2DM OA cartilage (0.57-fold Nrf-2 and 0.34-fold HO-1), and prostaglandin E2 (PGE2) release was increased in samples with low HO-1 expression. HG-exposed, IL-1β-stimulated chondrocytes had lower Nrf-2 levels in vitro, particularly in the nuclear fraction, than chondrocytes exposed to normal glucose (NG). Accordingly, HO-1 levels were also decreased (0.49-fold) in these cells. The HO-1 inducer cobalt protoporphyrin IX more efficiently attenuated PGE2 and IL-6 release in HG+IL-1β-treated cells than in NG+IL-1β-treated cells. Greater reductions in HO-1 expression and increase in PGE2/IL-6 production were observed in HG+IL-1β-stimulated chondrocytes from Nrf-2−/− mice than in chondrocytes from wild-type mice. We conclude that the Nrf-2/HO-1 axis is a critical pathway in the hyperglucidic-mediated dysregulation of chondrocytes. Impairments in this antioxidant system may explain the greater inflammatory responsiveness of OA cartilage from T2DM patients and may inform treatments of such patients.
Palabras chave
Diabetes
Heme oxygenase
Inflammation
Nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2)
Osteoarthritis
Heme oxygenase
Inflammation
Nuclear factor 2 (erythroid-derived 2-like factor) (NFE2L2) (Nrf2)
Osteoarthritis
Versión do editor
ISSN
0021-9258
1083-351X
1083-351X