{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:39:10Z","timestamp":1791355150936,"version":"4.3.1"},"reference-count":78,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,12,24]],"date-time":"2020-12-24T00:00:00Z","timestamp":1608768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Reduced vitamin D receptor (VDR) expression prompts skeletal muscle atrophy.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Atrophy occurs through catabolic processes, namely the induction of autophagy, while anabolism remains unchanged.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>In response to VDR\u2010knockdown mitochondrial function and related gene\u2010set expression is impaired.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>In vitro<\/jats:italic>\n                            VDR knockdown induces myogenic dysregulation occurring through impaired differentiation.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These results highlight the autonomous role the VDR has within skeletal muscle mass regulation.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Vitamin D deficiency is estimated to affect \u223c40% of the world's population and has been associated with impaired muscle maintenance. Vitamin D exerts its actions through the vitamin D receptor (VDR), the expression of which was recently confirmed in skeletal muscle, and its down\u2010regulation is linked to reduced muscle mass and functional decline. To identify potential mechanisms underlying muscle atrophy, we studied the impact of VDR knockdown (KD) on mature skeletal muscle\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and myogenic regulation\n                      <jats:italic>in vitro<\/jats:italic>\n                      in C2C12 cells. Male Wistar rats underwent\n                      <jats:italic>in vivo<\/jats:italic>\n                      electrotransfer (IVE) to knock down the VDR in hind\u2010limb tibialis anterior (TA) muscle for 10\u00a0days. Comprehensive metabolic and physiological analysis was undertaken to define the influence loss of the VDR on muscle fibre composition, protein synthesis, anabolic and catabolic signalling, mitochondrial phenotype and gene expression. Finally,\n                      <jats:italic>in vitro<\/jats:italic>\n                      lentiviral transfection was used to induce sustained VDR\u2010KD in C2C12 cells to analyse myogenic regulation. Muscle VDR\u2010KD elicited atrophy through a reduction in total protein content, resulting in lower myofibre area. Activation of autophagic processes was observed, with no effect upon muscle protein synthesis or anabolic signalling. Furthermore, RNA\u2010sequencing analysis identified systematic down\u2010regulation of multiple mitochondrial respiration\u2010related protein and genesets. Finally,\n                      <jats:italic>in vitro<\/jats:italic>\n                      VDR\u2010knockdown impaired myogenesis (cell cycling, differentiation and myotube formation). Together, these data indicate a fundamental regulatory role of the VDR in the regulation of myogenesis and muscle mass, whereby it acts to maintain muscle mitochondrial function and limit autophagy.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp280652","type":"journal-article","created":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T08:17:38Z","timestamp":1606810658000},"page":"963-979","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["The mechanisms of skeletal muscle atrophy in response to transient knockdown of the vitamin D receptor\n                    <i>in vivo<\/i>"],"prefix":"10.1113","volume":"599","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8236-681X","authenticated-orcid":false,"given":"Joseph J.","family":"Bass","sequence":"first","affiliation":[{"name":"MRC\/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC) School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abid A.","family":"Kazi","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Physiology Pennsylvania State University College of Medicine  Hershey PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2281-6479","authenticated-orcid":false,"given":"Colleen S.","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Sport and Health Sciences University of Exeter  Exeter UK"},{"name":"Living Systems Institute University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asif","family":"Nakhuda","sequence":"additional","affiliation":[{"name":"MRC\/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC) School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen P.","family":"Ashcroft","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences University of Birmingham  Birmingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Brook","sequence":"additional","affiliation":[{"name":"MRC\/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC) School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8808-8243","authenticated-orcid":false,"given":"Daniel J.","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"MRC\/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC) School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bethan E.","family":"Phillips","sequence":"additional","affiliation":[{"name":"MRC\/ARUK Centre for Musculoskeletal Ageing Research and National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre (BRC) School of Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Philp","sequence":"additional","affiliation":[{"name":"School of Sport, Exercise and Rehabilitation Sciences University of Birmingham  Birmingham UK"},{"name":"Mitochondrial Metabolism &amp; 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