caa a22 4500 605520518 CHVBK 20210128100735.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s00223-015-0054-x doi (NATIONALLICENCE)springer-10.1007/s00223-015-0054-x Vitamin D Receptor Ablation and Vitamin D Deficiency Result in Reduced Grip Strength, Altered Muscle Fibers, and Increased Myostatin in Mice [Elektronische Daten] [Christian Girgis, Kuan Cha, Peter Houweling, Renuka Rao, Nancy Mokbel, Mike Lin, Roderick Clifton-Bligh, Jenny Gunton] Vitamin D deficiency is associated with muscle weakness, pain, and atrophy. Serum vitamin D predicts muscle strength and age-related muscle changes. However, precise mechanisms by which vitamin D affects skeletal muscle are unclear. To address this question, this study characterizes the muscle phenotype and gene expression of mice with deletion of vitamin D receptor (VDRKO) or diet-induced vitamin D deficiency. VDRKO and vitamin D-deficient mice had significantly weaker grip strength than their controls. Weakness progressed with age and duration of vitamin D deficiency, respectively. Histological assessment showed that VDRKO mice had muscle fibers that were significantly smaller in size and displayed hyper-nuclearity. Real-time PCR also indicated muscle developmental changes in VDRKO mice with dysregulation of myogenic regulatory factors (MRFs) and increased myostatin in quadriceps muscle (>2-fold). Vitamin D-deficient mice also showed increases in myostatin and the atrophy marker E3-ubiqutin ligase MuRF1. As a potential explanation for grip strength weakness, both groups of mice had down-regulation of genes encoding calcium-handling and sarco-endoplasmic reticulum calcium transport ATPase (Serca) channels. This is the first report of reduced strength, morphological, and gene expression changes in VDRKO and vitamin D-deficient mice where confounding by calcium, magnesium, and phosphate have been excluded by direct testing. Although suggested in earlier in vitro work, this study is the first to report an in vivo association between vitamin D, myostatin, and the regulation of muscle mass. These findings support a direct role for vitamin D in muscle function and corroborate earlier work on the presence of VDR in this tissue. Springer Science+Business Media New York, 2015 Vitamin D nationallicence Vitamin D receptor nationallicence Skeletal muscle nationallicence Strength nationallicence Development nationallicence Aging nationallicence Girgis Christian Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut Cha Kuan Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut Houweling Peter Murdoch Childrens' Research Institute, Melbourne, VIC, Australia aut Rao Renuka Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut Mokbel Nancy Garvan Institute of Medical Research, Sydney, NSW, Australia aut Lin Mike Garvan Institute of Medical Research, Sydney, NSW, Australia aut Clifton-Bligh Roderick Faculty of Medicine, University of Sydney, Sydney, NSW, Australia aut Gunton Jenny Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut Calcified Tissue International Springer US; http://www.springer-ny.com 97/6(2015-12-01), 602-610 0171-967X 97:6<602 2015 97 223 https://doi.org/10.1007/s00223-015-0054-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00223-015-0054-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Girgis Christian Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Cha Kuan Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Houweling Peter Murdoch Childrens' Research Institute, Melbourne, VIC, Australia aut NATIONALLICENCE 700 1- Rao Renuka Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Mokbel Nancy Garvan Institute of Medical Research, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Lin Mike Garvan Institute of Medical Research, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Clifton-Bligh Roderick Faculty of Medicine, University of Sydney, Sydney, NSW, Australia aut NATIONALLICENCE 700 1- Gunton Jenny Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia aut NATIONALLICENCE 773 0- Calcified Tissue International Springer US; http://www.springer-ny.com 97/6(2015-12-01), 602-610 0171-967X 97:6<602 2015 97 223