Prevent Osteoarthritis (and Diabetes) by Increasing Net Antioxidant Capacity

Aging is a risk factor for osteoarthritis.

Diabetes is a risk factor for osteoarthritis.

Diabetes accelerates aging.

Why?

Net total antioxidant capacity decreases with both aging and diabetes.

Nrf2 increases net total antioxidant capacity.

In this study bolded  text showing DM vs DM- OA varied according to Nrf2 status and therefore net total antioxidant capacity varied!

How?

See preceding posts.

http://www.jbc.org/content/early/2017/07/06/jbc.M117.802157.short

The nuclear factor-erythroid 2-related factor/heme oxygenase-1 axis is critical for the inflammatory features of type 2 diabetes-associated osteoarthritis

Carlos Vaamonde-Garcia1,

1. Alice Courties2, 
2. Audrey Pigenet3, 
3. Marie-Charlotte Laiguillon3, 
4. Alain Sautet2, 
5. Xavier Houard3, 
6. Saadia Kerdine-R&oumlmer4, 
7. Rosa Meijide5, 
8. Francis Berenbaum2* and 
9. J&eacuter&eacutemie Sellam2

+ Author Affiliations

1. ↵* Corresponding author; email: francis.berenbaum@sat.aphp.fr

1. Author contributions: CV-G, AC, M-CL, XH, SK-R, RS, FB and JS were responsible for the study design, manuscript preparation, and data interpretation. AS organized and collected the human tissue samples and participated in designing the experiments with human tissue and in data interpretation. CV-G, AC and AP performed the experiments. SK-R was responsible for generating the Nrf-2-/- mice and was involved in data interpretation. All authors reviewed and approved the final manuscript.

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 vs. 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. A greater reduction 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.