Vitamin D Receptor Ablation and Vitamin D Deficiency Result in Reduced Grip Strength, Altered Muscle Fibers, and Increased Myostatin in Mice

Verfasser / Beitragende:
[Christian Girgis, Kuan Cha, Peter Houweling, Renuka Rao, Nancy Mokbel, Mike Lin, Roderick Clifton-Bligh, Jenny Gunton]
Ort, Verlag, Jahr:
2015
Enthalten in:
Calcified Tissue International, 97/6(2015-12-01), 602-610
Format:
Artikel (online)
ID: 605520518
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024 7 0 |a 10.1007/s00223-015-0054-x  |2 doi 
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245 0 0 |a Vitamin D Receptor Ablation and Vitamin D Deficiency Result in Reduced Grip Strength, Altered Muscle Fibers, and Increased Myostatin in Mice  |h [Elektronische Daten]  |c [Christian Girgis, Kuan Cha, Peter Houweling, Renuka Rao, Nancy Mokbel, Mike Lin, Roderick Clifton-Bligh, Jenny Gunton] 
520 3 |a 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. 
540 |a Springer Science+Business Media New York, 2015 
690 7 |a Vitamin D  |2 nationallicence 
690 7 |a Vitamin D receptor  |2 nationallicence 
690 7 |a Skeletal muscle  |2 nationallicence 
690 7 |a Strength  |2 nationallicence 
690 7 |a Development  |2 nationallicence 
690 7 |a Aging  |2 nationallicence 
700 1 |a Girgis  |D Christian  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
700 1 |a Cha  |D Kuan  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
700 1 |a Houweling  |D Peter  |u Murdoch Childrens' Research Institute, Melbourne, VIC, Australia  |4 aut 
700 1 |a Rao  |D Renuka  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
700 1 |a Mokbel  |D Nancy  |u Garvan Institute of Medical Research, Sydney, NSW, Australia  |4 aut 
700 1 |a Lin  |D Mike  |u Garvan Institute of Medical Research, Sydney, NSW, Australia  |4 aut 
700 1 |a Clifton-Bligh  |D Roderick  |u Faculty of Medicine, University of Sydney, Sydney, NSW, Australia  |4 aut 
700 1 |a Gunton  |D Jenny  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
773 0 |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 97/6(2015-12-01), 602-610  |x 0171-967X  |q 97:6<602  |1 2015  |2 97  |o 223 
856 4 0 |u https://doi.org/10.1007/s00223-015-0054-x  |q text/html  |z Onlinezugriff via DOI 
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900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00223-015-0054-x  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Girgis  |D Christian  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Cha  |D Kuan  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Houweling  |D Peter  |u Murdoch Childrens' Research Institute, Melbourne, VIC, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Rao  |D Renuka  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Mokbel  |D Nancy  |u Garvan Institute of Medical Research, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Lin  |D Mike  |u Garvan Institute of Medical Research, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Clifton-Bligh  |D Roderick  |u Faculty of Medicine, University of Sydney, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Gunton  |D Jenny  |u Westmead Millennium Institute, 176 Hawkesbury Rd, Westmead, 2145, Sydney, NSW, Australia  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Calcified Tissue International  |d Springer US; http://www.springer-ny.com  |g 97/6(2015-12-01), 602-610  |x 0171-967X  |q 97:6<602  |1 2015  |2 97  |o 223