{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:04:28Z","timestamp":1786133068531,"version":"build-2736575974"},"reference-count":74,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>\n                    Circulating levels of fibroblast growth factor 23 (FGF23) increase during the early stages of kidney disease, but the underlying mechanism remains incompletely characterized. We investigated the role of vitamin D metabolites in regulating intact FGF23 production in genetically modified mice without and with adenine-induced uremia. Exogenous calcitriol (1,25-dihydroxyvitamin D) and high circulating levels of calcidiol (25-hydroxyvitamin D) each increased serum FGF23 levels in wild-type mice and in mice with global deficiency of the Cyp27b1 gene encoding 25-hydroxyvitamin D 1-\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -hydroxylase, which produces 1,25-hydroxyvitamin D. Compared with wild-type mice, normal, or uremic mice lacking Cyp27b1 had lower levels of serum FGF23, despite having high concentrations of parathyroid hormone, but administration of exogenous 1,25-dihydroxyvitamin D increased FGF23 levels. Furthermore, raising serum calcium levels in Cyp27b1-depleted mice directly increased FGF23 levels and indirectly enhanced the action of ambient vitamin D metabolites\n                    <jats:italic toggle=\"yes\">via<\/jats:italic>\n                    the vitamin D receptor. In chromatin immunoprecipitation assays, 25-hydroxyvitamin D promoted binding of the vitamin D receptor and retinoid X receptor to the promoters of osteoblastic target genes. Conditional osteoblastic deletion of Cyp27b1 caused lower serum FGF23 levels, despite normal circulating levels of vitamin D metabolites. In adenine-induced uremia, only a modest increase in serum FGF23 levels occurred in mice with osteoblastic deletion of Cyp27b1 (12-fold) compared with a large increase (58-fold) in wild-type mice. Therefore, in addition to the direct effect of high circulating concentrations of 25-hydroxyvitamin D, local osteoblastic conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D appears to be an important positive regulator of FGF23 production, particularly in uremia.\n                  <\/jats:p>","DOI":"10.1681\/asn.2016010066","type":"journal-article","created":{"date-parts":[[2016,8,17]],"date-time":"2016-08-17T22:13:29Z","timestamp":1471472009000},"page":"586-597","source":"Crossref","is-referenced-by-count":62,"title":["Fibroblast Growth Factor 23 Regulation by Systemic and Local Osteoblast-Synthesized 1,25-Dihydroxyvitamin D"],"prefix":"10.1681","volume":"28","author":[{"given":"Loan","family":"Nguyen-Yamamoto","sequence":"first","affiliation":[{"name":"Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Karaplis","sequence":"additional","affiliation":[{"name":"Department of Medicine, Sir Mortimer B. Davis Jewish General Hospital, McGill University, Montreal, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"St\u2013Arnaud","sequence":"additional","affiliation":[{"name":"Medicine,"},{"name":"Surgery, and"},{"name":"Human Genetics, and"},{"name":"Research Centre, Shriners Hospital for Children, Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Goltzman","sequence":"additional","affiliation":[{"name":"Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,8,17]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s00467-012-2309-3","article-title":"FGF23 production by osteocytes.","volume":"28","author":"Bonewald","year":"2013","journal-title":"Pediatr Nephrol"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/81664","article-title":"Autosomal 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