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.
SourceAvailable from: Christian M Girgis[Show abstract] [Hide abstract]
ABSTRACT: Beyond the established roles of vitamin D in bone and mineral homeostasis, we are becoming increasingly aware of its diverse effects in skeletal muscle. Subjects with severe vitamin D deficiency or mutations of the vitamin D receptor develop generalized atrophy of muscle and bone, suggesting coordinated effects of vitamin D in musculoskeletal physiology. At a mechanistic level, vitamin D exerts wide-ranging effects in muscle and bone calcium handling, differentiation and development. Vitamin D also modulates muscle and bone-derived hormones, facilitating cross-talk between these tissues. In this review, we discuss emerging evidence that vitamin D regulates bone and muscle in a direct, integrated fashion, positioning the vitamin D pathway as a potential therapeutic target for musculoskeletal diseases. Copyright © 2015. Published by Elsevier Inc.Bone 03/2015; DOI:10.1016/j.bone.2015.02.029 · 4.46 Impact Factor
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ABSTRACT: The aim of the present study was to investigate the association between vitamin D receptor (VDR) gene polymorphisms and musculoskeletal injury (MI) in elite football players. In total, 54 male professional football players were recruited from an official Italian professional championship team between 2009 and 2013. The cohort was genotyped for the ApaI, BsmI and FokI polymorphisms and MI data were collected over four football seasons. No significant differences were identified among the genotypes in the incidence rates or severity of MI (P=0.254). In addition, no significant associations were observed between VDR polymorphisms and MI phenotypes (P=0.460). However, the results of the casewise multiple regression analysis indicated that the ApaI genotypes accounted for 18% of injury severity (P=0.002). Therefore, while the BsmI and FokI polymorphisms did not appear to be associated with the severity or incidence of MI, the ApaI genotypes may have influenced the severity of muscle injury in top-level football players.Experimental and therapeutic medicine 04/2015; 9:1974. · 0.94 Impact Factor
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ABSTRACT: Recently, special attention has been given to the role of vitamin D on the pathogenesis and therapy of sarcopenia in postmenopausal women. To elucidate the role of vitamin D with respect to sarcopenia in postmenopausal women, providing current evidence from both molecular and clinical studies. Systematic search to PubMed and Medline databases for publications reporting data on the role of vitamin D in sarcopenia. Sarcopenia has a high prevalence in postmenopausal women, leading to mobility restriction, functional impairment, physical disability and fractures. Accumulating evidence from molecular and clinical studies suggest that vitamin D deficiency is associated with sarcopenic status in elderly women independent of body composition, diet and hormonal status. Current data, but not in a uniform way, provide evidence about the beneficial effect of vitamin D supplementation on muscle strength, physical performance and prevention of falls and fractures in elderly female populations. It is still unclear if and to what extent treatment modalities, such as dose, mode of administration and duration of supplementation, could influence treatment outcome. Studies with superior methodological characteristics are needed in order to establish a role for vitamin D on the treatment of sarcopenia in postmenopausal women. Copyright © 2015. Published by Elsevier Ireland Ltd.Maturitas 03/2015; DOI:10.1016/j.maturitas.2015.03.014 · 2.86 Impact Factor