VDR and CYP27B1 are expressed in C2C12 cells and regenerating skeletal muscle: potential role in suppression of myoblast proliferation.
ABSTRACT 1α,25(OH)(2)D(3), the active form of vitamin D(3), has been reported to regulate the cell biology of skeletal muscle. However, there has been some controversy about the expression of the vitamin D receptor (VDR) and thus the potential role of vitamin D(3) in skeletal muscle. In this study, we isolated and sequenced the full-length Vdr and Cyp27b1 transcripts in C2C12 myoblasts and myotubes. Western blots and immunocytochemistry confirmed protein expression in both myoblasts and myotubes clearly demonstrating that C2C12 cells express VDR and CYP27B1. To determine the vitamin D(3) action, we found that C2C12 myoblasts treated with either 1α,25(OH)(2)D(3) or 25(OH)D(3) inhibited cell proliferation and this was associated with increased Vdr expression. The observation that treatment of C2C12 myoblasts with the inactive form of vitamin D(3), [25(OH)D(3)], inhibited proliferation suggested that CYP27B1 was functionally active. We used small interfering RNA to knock down Cyp27b1 in myoblasts, and cells were treated with 25(OH)D(3). The growth-suppressive effects of 25(OH)D(3) were abolished, suggesting that CYP27B1 in myoblasts is necessary for the ability of 25(OH)D(3) to affect cell proliferation. Finally, we analyzed expression of VDR and CYP27B1 in regenerating skeletal muscle in vivo. We found that expression of VDR and CYP27B1 increased significantly at day 7 of regeneration, and these results confirm the expression of Vdr and Cyp27b1 in vivo and suggest a potential role for vitamin D(3) in skeletal muscle regeneration following injury.
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ABSTRACT: Vitamin D may be a regulator of skeletal muscle function, although human trials investigating this hypothesis are limited to predominantly elderly populations. We aimed to assess the effect of oral vitamin D3 in healthy young males upon skeletal muscle function. Participants (n = 29) received an oral dose of 10,000 IU day(-1) vitamin D3 (VITD) or a visually identical placebo (PLB) for 3 months. Serum 25[OH]D and intact parathyroid hormone (iPTH) were measured at baseline and at week 4, 8 and 12. Muscle function was assessed in n = 22 participants by isokinetic dynamometry and percutaneous isometric electromyostimulation at baseline and at week 6 and 12. Baseline mean total serum 25[OH]D was 40 ± 17 and 41 ± 20 nmol L(-1) for PLB and VITD, respectively. VITD showed a significant improvement in total 25[OH]D at week 4 (150 ± 31 nmol L(-1)) that remained elevated throughout the trial (P < 0.005). Contrastingly, PLB showed a significant decrease in 25[OH]D at week 12 (25 ± 15 nmol L(-1)) compared with baseline. Despite marked increases in total serum 25[OH]D in VITD and a decrease in PLB, there were no significant changes in any of the muscle function outcome measures at week 6 or 12 for either group (P > 0.05). Elevating total serum 25[OH]D to concentrations > 120 nmol L(-1) has no effect on skeletal muscle function. We postulate that skeletal muscle function is only perturbed in conditions of severe deficiency (<12.5 nmol L(-1)).Arbeitsphysiologie 03/2014; · 2.66 Impact Factor
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ABSTRACT: ABSTRACT Aim: The aim of this study is to analyze the effect of vitamin D deficiency on muscle strength and quality of life in postmenopausal women. Methods: Self sufficient community dwelling postmenopausal women over 55 attending to Physical Medicine and Rehabilitation out patient clinic were included in the study. 25(OH) vitamin D levels below 20 ng/ml were accepted as vitamin D defiency. A computerized isokinetic dynamometer (Cybex 770 Norm, Lumex Inc., Ronkonkoma, NY) was used for testing knee extensor muscle strength. Results: Forty-nine postmenopausal women with median age 64.3 (59.0-69.5) [median (Inter Quartile Range)] were included in the study. Vitamin D deficiency was detected in 49% of participants. There was no relation between vitamin D deficiency and knee muscle strength in both right and left legs. Vitamin D deficiency was found to be not associated with none of the domains of SF-36. Conclusions: Vitamin D deficiency is not related with decreased muscle strength and lowered quality of life in postmenopausal women. Other factors rather than vitamin D deficiency should be investigated for illuminating causalities of these three common clinical conditions.Climacteric 03/2014; · 1.96 Impact Factor
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ABSTRACT: In this review, we summarize current evidence for a direct effect of vitamin D on skeletal muscle. A number of studies identify the receptor for 1,25-dihydroxyvitamin-D3 (VDR) and the enzyme CYP27B1 (1-α-hydroxylase) in muscle. We hypothesize that vitamin D acts on myocytes via the VDR, and we examine proposed effects on myocyte proliferation, differentiation, growth and inflammation. A summary of evidence for a role of vitamin D and VDR in skeletal muscle, highlighting molecular physiology and biological pathways.Exercise and sport sciences reviews 02/2014; · 3.23 Impact Factor