title: The vitamin D receptor (VDR) is expressed in skeletal muscle of male mice and modulates 25-hydroxyvitamin D (25OHD) uptake in myofibers.
abstract: Vitamin D deficiency is associated with a range of muscle disorders, including myalgia, muscle weakness, and falls. In humans, polymorphisms of the vitamin D receptor (VDR) gene are associated with variations in muscle strength, and in mice, genetic ablation of VDR results in muscle fiber atrophy and motor deficits. However, mechanisms by which VDR regulates muscle function and morphology remain unclear. A crucial question is whether VDR is expressed in skeletal muscle and directly alters muscle physiology. Using PCR, Western blotting, and immunohistochemistry (VDR-D6 antibody), we detected VDR in murine quadriceps muscle. Detection by Western blotting was dependent on the use of hyperosmolar lysis buffer. Levels of VDR in muscle were low compared with duodenum and dropped progressively with age. Two in vitro models, C2C12 and primary myotubes, displayed dose- and time-dependent increases in expression of both VDR and its target gene CYP24A1 after 1,25(OH)2D (1,25 dihydroxyvitamin D) treatment. Primary myotubes also expressed functional CYP27B1 as demonstrated by luciferase reporter studies, supporting an autoregulatory vitamin D-endocrine system in muscle. Myofibers isolated from mice retained tritiated 25-hydroxyvitamin D3, and this increased after 3 hours of pretreatment with 1,25(OH)2D (0.1 nM). No such response was seen in myofibers from VDR knockout mice. In summary, VDR is expressed in skeletal muscle, and vitamin D regulates gene expression and modulates ligand-dependent uptake of 25-hydroxyvitamin D3 in primary myofibers.
authors.affiliation: Garvan Institute of Medical Research (C.M.G., N.M., K.M.C., J.E.G.), Sydney, New South Wales, Australia 2010; Faculties of Medicine (C.M.G., M.A., R.S.M., R.J.C.-B., J.E.G.) and Veterinary Science (D.R.F.) University of Sydney, Sydney, New South Wales, Australia 2145; Bosch Institute (M.A., R.S.M.), University of Sydney, Sydney, New South Wales, Australia 2006; Murdoch Childrens Research Institute (P.J.H.), Melbourne, Victoria, Australia 3000; The Kolling Institute of Medical Research (R.J.C.-B.), Sydney, New South Wales, Australia 2065; Royal North Shore Hospital (R.J.C.-B.), Sydney, New South Wales, Australia 2065; Department of Endocrinology and Diabetes (J.E.G.), Westmead Hospital, Sydney, New South Wales, Australia 2145; and St Vincent's Clinical School (J.E.G.), University of New South Wales, Sydney, New South Wales, Australia 2010.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Girgis
authors.forename: Nancy
authors.initials: N
authors.lastname: Mokbel
authors.forename: Kuan Minn
authors.initials: KM
authors.lastname: Cha
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houweling
authors.forename: Myriam
authors.initials: M
authors.lastname: Abboud
authors.forename: David R
authors.initials: DR
authors.lastname: Fraser
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Mason
authors.forename: Roderick J
authors.initials: RJ
authors.lastname: Clifton-Bligh
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Gunton
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018167:Receptors, Calcitriol; D014807:Vitamin D; C104450:25-hydroxyvitamin D