Cargando…

The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers

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 an...

Descripción completa

Detalles Bibliográficos
Autores principales: Girgis, Christian M., Mokbel, Nancy, Cha, Kuan Minn, Houweling, Peter J., Abboud, Myriam, Fraser, David R., Mason, Rebecca S., Clifton-Bligh, Roderick J., Gunton, Jenny E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207908/
https://www.ncbi.nlm.nih.gov/pubmed/24949660
http://dx.doi.org/10.1210/en.2014-1016
_version_ 1782341051403468800
author Girgis, Christian M.
Mokbel, Nancy
Cha, Kuan Minn
Houweling, Peter J.
Abboud, Myriam
Fraser, David R.
Mason, Rebecca S.
Clifton-Bligh, Roderick J.
Gunton, Jenny E.
author_facet Girgis, Christian M.
Mokbel, Nancy
Cha, Kuan Minn
Houweling, Peter J.
Abboud, Myriam
Fraser, David R.
Mason, Rebecca S.
Clifton-Bligh, Roderick J.
Gunton, Jenny E.
author_sort Girgis, Christian M.
collection PubMed
description 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)(2)D (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 D(3), and this increased after 3 hours of pretreatment with 1,25(OH)(2)D (0.1nM). 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 D(3) in primary myofibers.
format Online
Article
Text
id pubmed-4207908
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Endocrine Society
record_format MEDLINE/PubMed
spelling pubmed-42079082014-11-04 The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers Girgis, Christian M. Mokbel, Nancy Cha, Kuan Minn Houweling, Peter J. Abboud, Myriam Fraser, David R. Mason, Rebecca S. Clifton-Bligh, Roderick J. Gunton, Jenny E. Endocrinology Calcium-Regulating Hormones 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)(2)D (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 D(3), and this increased after 3 hours of pretreatment with 1,25(OH)(2)D (0.1nM). 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 D(3) in primary myofibers. Endocrine Society 2014-09 2014-06-20 /pmc/articles/PMC4207908/ /pubmed/24949660 http://dx.doi.org/10.1210/en.2014-1016 Text en Copyright © 2014 by the Endocrine Society This article has been published under the terms of the Creative Commons Attribution License (CC-BY (http://creativecommons.org/licenses/by/3.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Copyright for this article is retained by the author(s). Author(s) grant(s) the Endocrine Society the exclusive right to publish the article and identify itself as the original publisher.
spellingShingle Calcium-Regulating Hormones
Girgis, Christian M.
Mokbel, Nancy
Cha, Kuan Minn
Houweling, Peter J.
Abboud, Myriam
Fraser, David R.
Mason, Rebecca S.
Clifton-Bligh, Roderick J.
Gunton, Jenny E.
The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title_full The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title_fullStr The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title_full_unstemmed The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title_short The Vitamin D Receptor (VDR) Is Expressed in Skeletal Muscle of Male Mice and Modulates 25-Hydroxyvitamin D (25OHD) Uptake in Myofibers
title_sort vitamin d receptor (vdr) is expressed in skeletal muscle of male mice and modulates 25-hydroxyvitamin d (25ohd) uptake in myofibers
topic Calcium-Regulating Hormones
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4207908/
https://www.ncbi.nlm.nih.gov/pubmed/24949660
http://dx.doi.org/10.1210/en.2014-1016
work_keys_str_mv AT girgischristianm thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT mokbelnancy thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT chakuanminn thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT houwelingpeterj thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT abboudmyriam thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT fraserdavidr thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT masonrebeccas thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT cliftonblighroderickj thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT guntonjennye thevitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT girgischristianm vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT mokbelnancy vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT chakuanminn vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT houwelingpeterj vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT abboudmyriam vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT fraserdavidr vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT masonrebeccas vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT cliftonblighroderickj vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers
AT guntonjennye vitamindreceptorvdrisexpressedinskeletalmuscleofmalemiceandmodulates25hydroxyvitamind25ohduptakeinmyofibers