{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:54:17Z","timestamp":1785200057458,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","award":["21\u201044"],"award-info":[{"award-number":["21\u201044"]}],"id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09289"],"award-info":[{"award-number":["21K09289"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.028, <jats:italic>N<\/jats:italic>\u00a0=\u00a03), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1\u03b1,25(OH)2D3, 100\u00a0nM) for 7\u00a0days, and adipogenicity was evaluated based on adipogenic marker expression. For <jats:italic>in vivo<\/jats:italic> analysis, tamoxifen\u2010inducible MP\u2010specific VDR\u2010deficient (<jats:italic>Vdr<\/jats:italic><jats:sup>MPcKO<\/jats:sup>) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, <jats:italic>Vdr<\/jats:italic><jats:sup>MPcKO<\/jats:sup> male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross\u2010sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3\u00a0weeks after operation (<jats:italic>N<\/jats:italic>\u00a0=\u00a03\u20134). In addition, a vitamin D\u2010deficient diet was provided to wild\u2010type male mice (3 and 20\u00a0months of age, <jats:italic>N<\/jats:italic>\u00a0=\u00a05) for 3\u00a0months to investigate whether vitamin D deficiency causes IMAT formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1\u2010mediated transcriptional modifications of early adipogenic factors such as PPAR\u03b3 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0031) and C\/EBP\u03b1 (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0027), whereas VDR\u2010deficient MPs derived from <jats:italic>Vdr<\/jats:italic><jats:sup>MPcKO<\/jats:sup> mice differentiated into adipocytes even in the presence of vitamin D (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0044, Oil\u2010Red O<jats:sup>+<\/jats:sup> area). In consistency with <jats:italic>in\u2010vitro<\/jats:italic> findings, <jats:italic>Vdr<\/jats:italic><jats:sup>MPcKO<\/jats:sup> mice and mice fed a vitamin D\u2010deficient diet exhibited fat deposition in atrophied (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0311) and aged (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0216) skeletal muscle, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13448","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T07:45:59Z","timestamp":1711525559000},"page":"907-918","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Lack of vitamin D signalling in mesenchymal progenitors causes fatty infiltration in muscle"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1825-6923","authenticated-orcid":false,"given":"Tohru","family":"Hosoyama","sequence":"first","affiliation":[{"name":"Department of Musculoskeletal Disease, Research Institute National Center for Geriatrics and Gerontology  Obu 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