Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats

BACKGROUND: The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite...

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Published in:Nutrition & metabolism 2014-09, Vol.11 (1), p.47-47, Article 47
Main Authors: Domingues-Faria, Carla, Chanet, Audrey, Salles, Jérôme, Berry, Alexandre, Giraudet, Christophe, Patrac, Véronique, Denis, Philippe, Bouton, Katia, Goncalves-Mendes, Nicolas, Vasson, Marie-Paule, Boirie, Yves, Walrand, Stéphane
Format: Article
Language:English
Subjects:
Age
Aging
Analysis
Cell cycle
Cell growth
cell proliferation
correlation
elderly
Food and Nutrition
Gene expression
genes
Health aspects
Hypotheses
Life Sciences
messenger RNA
muscle strength
muscles
Musculoskeletal system
Nutrition
Older people
proliferating cell nuclear antigen
protein synthesis
Proteins
quantitative polymerase chain reaction
rats
Rodents
sarcopenia
skeletal muscle
Studies
t-test
Transcription factors
Vitamin D
Vitamin D deficiency
Vitamin deficiency
vitamin status
Western blotting
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cited_by cdi_FETCH-LOGICAL-b639t-3af557a09728799f9e51829442fe7f9c46e578482d2567d23346074101e802f73
cites cdi_FETCH-LOGICAL-b639t-3af557a09728799f9e51829442fe7f9c46e578482d2567d23346074101e802f73
container_end_page 47
container_issue 1
container_start_page 47
container_title Nutrition & metabolism
container_volume 11
creator Domingues-Faria, Carla
Chanet, Audrey
Salles, Jérôme
Berry, Alexandre
Giraudet, Christophe
Patrac, Véronique
Denis, Philippe
Bouton, Katia
Goncalves-Mendes, Nicolas
Vasson, Marie-Paule
Boirie, Yves
Walrand, Stéphane
description BACKGROUND: The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle. METHODS: 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student’s t-test was performed to test the effect of the experimental conditions. RESULTS: Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p 
doi_str_mv 10.1186/1743-7075-11-47
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Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle. METHODS: 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student’s t-test was performed to test the effect of the experimental conditions. RESULTS: Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p &lt; 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p &lt; 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p &lt; 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p &lt; 0.05) and its target Hes1 (-35%, p &lt; 0.05). CONCLUSIONS: A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.</description><identifier>ISSN: 1743-7075</identifier><identifier>EISSN: 1743-7075</identifier><identifier>DOI: 10.1186/1743-7075-11-47</identifier><identifier>PMID: 25317198</identifier><language>eng</language><publisher>England: Springer-Verlag</publisher><subject>Age ; Aging ; Analysis ; Cell cycle ; Cell growth ; cell proliferation ; correlation ; elderly ; Food and Nutrition ; Gene expression ; genes ; Health aspects ; Hypotheses ; Life Sciences ; messenger RNA ; muscle strength ; muscles ; Musculoskeletal system ; Nutrition ; Older people ; proliferating cell nuclear antigen ; protein synthesis ; Proteins ; quantitative polymerase chain reaction ; rats ; Rodents ; sarcopenia ; skeletal muscle ; Studies ; t-test ; Transcription factors ; Vitamin D ; Vitamin D deficiency ; Vitamin deficiency ; vitamin status ; Western blotting</subject><ispartof>Nutrition &amp; metabolism, 2014-09, Vol.11 (1), p.47-47, Article 47</ispartof><rights>COPYRIGHT 2014 BioMed Central Ltd.</rights><rights>2014 Domingues-Faria et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Domingues-Faria et al.; licensee BioMed Central Ltd. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b639t-3af557a09728799f9e51829442fe7f9c46e578482d2567d23346074101e802f73</citedby><cites>FETCH-LOGICAL-b639t-3af557a09728799f9e51829442fe7f9c46e578482d2567d23346074101e802f73</cites><orcidid>0000-0002-1787-5802 ; 0000-0003-0693-9433 ; 0000-0002-3999-1599 ; 0000-0002-4349-3664</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195890/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1610393131?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25317198$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01223538$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Domingues-Faria, Carla</creatorcontrib><creatorcontrib>Chanet, Audrey</creatorcontrib><creatorcontrib>Salles, Jérôme</creatorcontrib><creatorcontrib>Berry, Alexandre</creatorcontrib><creatorcontrib>Giraudet, Christophe</creatorcontrib><creatorcontrib>Patrac, Véronique</creatorcontrib><creatorcontrib>Denis, Philippe</creatorcontrib><creatorcontrib>Bouton, Katia</creatorcontrib><creatorcontrib>Goncalves-Mendes, Nicolas</creatorcontrib><creatorcontrib>Vasson, Marie-Paule</creatorcontrib><creatorcontrib>Boirie, Yves</creatorcontrib><creatorcontrib>Walrand, Stéphane</creatorcontrib><title>Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats</title><title>Nutrition &amp; metabolism</title><addtitle>Nutr Metab (Lond)</addtitle><description>BACKGROUND: The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle. METHODS: 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student’s t-test was performed to test the effect of the experimental conditions. RESULTS: Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p &lt; 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p &lt; 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p &lt; 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p &lt; 0.05) and its target Hes1 (-35%, p &lt; 0.05). CONCLUSIONS: A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.</description><subject>Age</subject><subject>Aging</subject><subject>Analysis</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>cell proliferation</subject><subject>correlation</subject><subject>elderly</subject><subject>Food and Nutrition</subject><subject>Gene expression</subject><subject>genes</subject><subject>Health aspects</subject><subject>Hypotheses</subject><subject>Life Sciences</subject><subject>messenger RNA</subject><subject>muscle strength</subject><subject>muscles</subject><subject>Musculoskeletal system</subject><subject>Nutrition</subject><subject>Older people</subject><subject>proliferating cell nuclear antigen</subject><subject>protein synthesis</subject><subject>Proteins</subject><subject>quantitative polymerase chain reaction</subject><subject>rats</subject><subject>Rodents</subject><subject>sarcopenia</subject><subject>skeletal muscle</subject><subject>Studies</subject><subject>t-test</subject><subject>Transcription factors</subject><subject>Vitamin D</subject><subject>Vitamin D deficiency</subject><subject>Vitamin deficiency</subject><subject>vitamin status</subject><subject>Western blotting</subject><issn>1743-7075</issn><issn>1743-7075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><recordid>eNp1kk1v1DAQhiMEoqVw5gaWuNBDWo-dxPYFaSkfrbQCiVKultdxsi5JvNhOl_33ONqydKsiH2zNPPPOeGay7CXgEwBenQIraM4wK3OAvGCPssOd5fGd90H2LIRrjCktBH6aHZCSAgPBD7Puh42qtwP6gGrTWG3NoDeodush96YdOxVNQF9c1Eu0UnG5Vhuk3RC9XYzRDi2KDoWfpjNRdagfg-4MUtG71XKDkqjrarS2ISqPvIrhefakUV0wL27vo-zq08fvZ-f5_Ovni7PZPF9UVMScqqYsmcKCEc6EaIQpgRNRFKQxrBG6qEzJeMFJTcqK1ST9qsKsAAyGY9IwepS92-quxkVvam1SwaqTK2975TfSKSv3PYNdytbdyAJEyQVOAsdbgeW9sPPZXE42DITQkvIbSOz7Lbuw7j_J9j3a9XKajJwmIwFkMVX89rZi736NJkTZ26BN16nBuDFIqIAIXgmYantzD712ox9SPycKU0GBwj-qVZ2Rdmhcyq0nUTkrqah4kTqWqJMHqHRq09s057QRyb4XcLwXMO2C-R1bNYYgLy6_7bOnW1Z7F4I3za4ngOW0vQ904dXdue34v-uagNdboFFOqtbbIK8uCYYSY8wxZoz-AaqS8KQ</recordid><startdate>20140930</startdate><enddate>20140930</enddate><creator>Domingues-Faria, Carla</creator><creator>Chanet, Audrey</creator><creator>Salles, Jérôme</creator><creator>Berry, Alexandre</creator><creator>Giraudet, Christophe</creator><creator>Patrac, Véronique</creator><creator>Denis, Philippe</creator><creator>Bouton, Katia</creator><creator>Goncalves-Mendes, Nicolas</creator><creator>Vasson, Marie-Paule</creator><creator>Boirie, Yves</creator><creator>Walrand, Stéphane</creator><general>Springer-Verlag</general><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>FBQ</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>ISR</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TS</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1787-5802</orcidid><orcidid>https://orcid.org/0000-0003-0693-9433</orcidid><orcidid>https://orcid.org/0000-0002-3999-1599</orcidid><orcidid>https://orcid.org/0000-0002-4349-3664</orcidid></search><sort><creationdate>20140930</creationdate><title>Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats</title><author>Domingues-Faria, Carla ; Chanet, Audrey ; Salles, Jérôme ; Berry, Alexandre ; Giraudet, Christophe ; Patrac, Véronique ; Denis, Philippe ; Bouton, Katia ; Goncalves-Mendes, Nicolas ; Vasson, Marie-Paule ; Boirie, Yves ; Walrand, Stéphane</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b639t-3af557a09728799f9e51829442fe7f9c46e578482d2567d23346074101e802f73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Age</topic><topic>Aging</topic><topic>Analysis</topic><topic>Cell cycle</topic><topic>Cell growth</topic><topic>cell proliferation</topic><topic>correlation</topic><topic>elderly</topic><topic>Food and Nutrition</topic><topic>Gene expression</topic><topic>genes</topic><topic>Health aspects</topic><topic>Hypotheses</topic><topic>Life Sciences</topic><topic>messenger RNA</topic><topic>muscle strength</topic><topic>muscles</topic><topic>Musculoskeletal system</topic><topic>Nutrition</topic><topic>Older people</topic><topic>proliferating cell nuclear antigen</topic><topic>protein synthesis</topic><topic>Proteins</topic><topic>quantitative polymerase chain reaction</topic><topic>rats</topic><topic>Rodents</topic><topic>sarcopenia</topic><topic>skeletal muscle</topic><topic>Studies</topic><topic>t-test</topic><topic>Transcription factors</topic><topic>Vitamin D</topic><topic>Vitamin D deficiency</topic><topic>Vitamin deficiency</topic><topic>vitamin status</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Domingues-Faria, Carla</creatorcontrib><creatorcontrib>Chanet, Audrey</creatorcontrib><creatorcontrib>Salles, Jérôme</creatorcontrib><creatorcontrib>Berry, Alexandre</creatorcontrib><creatorcontrib>Giraudet, Christophe</creatorcontrib><creatorcontrib>Patrac, Véronique</creatorcontrib><creatorcontrib>Denis, Philippe</creatorcontrib><creatorcontrib>Bouton, Katia</creatorcontrib><creatorcontrib>Goncalves-Mendes, Nicolas</creatorcontrib><creatorcontrib>Vasson, Marie-Paule</creatorcontrib><creatorcontrib>Boirie, Yves</creatorcontrib><creatorcontrib>Walrand, Stéphane</creatorcontrib><collection>AGRIS</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium &amp; 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metabolism</jtitle><addtitle>Nutr Metab (Lond)</addtitle><date>2014-09-30</date><risdate>2014</risdate><volume>11</volume><issue>1</issue><spage>47</spage><epage>47</epage><pages>47-47</pages><artnum>47</artnum><issn>1743-7075</issn><eissn>1743-7075</eissn><abstract>BACKGROUND: The diminished ability of aged muscle to self-repair is a factor behind sarcopenia and contributes to muscle atrophy. Muscle repair depends on satellite cells whose pool size is diminished with aging. A reduction in Notch pathway activity may explain the age-related decrease in satellite cell proliferation, as this pathway has been implicated in satellite cell self-renewal. Skeletal muscle is a target of vitamin D which modulates muscle cell proliferation and differentiation in vitro and stimulates muscle regeneration in vivo. Vitamin D status is positively correlated to muscle strength/function, and elderly populations develop a vitamin D deficiency. The aim of this study was to evaluate how vitamin D deficiency induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential in muscle. METHODS: 15-month-old male rats were vitamin D-depleted or not (control) for 9 months (n = 10 per group). Rats were 24-month-old at the end of the experiment. Gene and/or protein expression of markers of proliferation, or modulating proliferation, and of Notch signalling pathway were studied in the tibialis anterior muscle by qPCR and western blot. An unpaired student’s t-test was performed to test the effect of the experimental conditions. RESULTS: Vitamin D depletion led to a drop in concentrations of plasma 25-hydroxyvitamin D in depleted rats compared to controls (-74%, p &lt; 0.01). Tibialis anterior weight was decreased in D-depleted rats (-25%, p &lt; 0.05). The D-depleted group showed -39%, -31% drops in expression of two markers known to modulate proliferation (Bmp4, Fgf-2 mRNA levels) and -56% drop in one marker of cell proliferation (PCNA protein expression) compared to controls (p &lt; 0.05). Notch pathway activity was blunted in tibialis anterior of D-depleted rats compared to controls, seen as a down-regulation of cleaved Notch (-53%, p &lt; 0.05) and its target Hes1 (-35%, p &lt; 0.05). CONCLUSIONS: A 9-month vitamin D depletion induced vitamin D deficiency in old rats. Vitamin D depletion induces skeletal muscle atrophy in old rats through a reduction in Notch pathway activity and proliferation potential. Vitamin D deficiency could aggravate the age-related decrease in muscle regeneration capacity.</abstract><cop>England</cop><pub>Springer-Verlag</pub><pmid>25317198</pmid><doi>10.1186/1743-7075-11-47</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0002-1787-5802</orcidid><orcidid>https://orcid.org/0000-0003-0693-9433</orcidid><orcidid>https://orcid.org/0000-0002-3999-1599</orcidid><orcidid>https://orcid.org/0000-0002-4349-3664</orcidid><oa>free_for_read</oa></addata></record>
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ispartof Nutrition & metabolism, 2014-09, Vol.11 (1), p.47-47, Article 47
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1743-7075
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source Open Access: PubMed Central; Publicly Available Content Database
subjects Age
Aging
Analysis
Cell cycle
Cell growth
cell proliferation
correlation
elderly
Food and Nutrition
Gene expression
genes
Health aspects
Hypotheses
Life Sciences
messenger RNA
muscle strength
muscles
Musculoskeletal system
Nutrition
Older people
proliferating cell nuclear antigen
protein synthesis
Proteins
quantitative polymerase chain reaction
rats
Rodents
sarcopenia
skeletal muscle
Studies
t-test
Transcription factors
Vitamin D
Vitamin D deficiency
Vitamin deficiency
vitamin status
Western blotting
title Vitamin D deficiency down-regulates Notch pathway contributing to skeletal muscle atrophy in old wistar rats
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