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Nutr Metab (Lond). 2014 Sep 30;11(1):47. doi: 10.1186/1743-7075-11-47. eCollection 2014.

Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats.

Author information

1
Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
2
Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
3
Université d'Auvergne, Unité de Nutrition Humaine, Installation Expérimentale de Nutrition, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; INRA, UMR1019, UNH, CRNH Auvergne, 63000 Clermont-Ferrand, France.
4
Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France.
5
Université d'Auvergne, Unité de Nutrition Humaine, Equipe ECREIN, CLARA, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; Centre Jean Perrin, Unité de Nutrition, 63000 Clermont-Ferrand, France.
6
Université d'Auvergne, Unité de Nutrition Humaine, Equipe NuTriM, CRNH Auvergne; INRA, UMR 1019, UNH, CRNH Auvergne, Clermont Université, 63000 Clermont-Ferrand, France ; CHU Clermont-Ferrand, Service de Nutrition Clinique, 63003 Clermont-Ferrand, France.

Abstract

BACKGROUND:

The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle.

METHODS:

15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student's t-test was performed to test the effect of the experimental conditions.

RESULTS:

Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p < 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p < 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p < 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p < 0.05) and its target Hes1 (-35%, p < 0.05).

CONCLUSIONS:

A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.

KEYWORDS:

Aging; Notch signalling; Skeletal muscle atrophy; Vitamin D deficiency

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