{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:18:33Z","timestamp":1784557113648,"version":"3.55.0"},"reference-count":39,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,7]]},"abstract":"<jats:p>\n                    The active form of vitamin D3 (1\u03b1,25(OH)\n                    <jats:sub>2<\/jats:sub>\n                    D\n                    <jats:sub>3<\/jats:sub>\n                    , also known as calcitriol) controls the expression of target genes via the vitamin D receptor (VDR). Vitamin D-dependent rickets type II (VDDRII) is a congenital disease caused by inactivating mutations in the\n                    <jats:italic>VDR<\/jats:italic>\n                    . The condition is treated with high doses of calcitriol, but the therapeutic effects of other synthetic VD\n                    <jats:sub>3<\/jats:sub>\n                    analogs have not yet been investigated. In the present study, we analyzed the transcriptional activity of seven different VD\n                    <jats:sub>3<\/jats:sub>\n                    analogs with VDRs carrying ligand-binding domain mutations identified in VDDRII patients. Wild-type VDR (WT-VDR) and seven mutant VDRs were expressed in TSA201 human embryonic kidney cells, HepG2 human liver cancer cells, and MC3T3-E1 mouse calvaria cells, and their transcriptional activation with VD\n                    <jats:sub>3<\/jats:sub>\n                    analogs were analyzed by performing transient expression assays, western blotting, and quantitative real-time PCR. The results demonstrated that falecalcitriol stimulated significantly higher transcriptional activation of the WT-VDR and some mutant VDRs than did calcitriol. Calcitriol showed almost no transcriptional activation of the VDR with the I268T mutation identified in a severe case of VDDRII, whereas falecalcitriol caused a dose-dependent increase in the activation of this mutant VDR. Our findings demonstrate that falecalcitriol has a VDR activation profile distinct from that of calcitriol and may exhibit therapeutic effects even on difficult-to-treat VDDRII cases resistant to calcitriol. It is also possible that VDDRII patients responding to high doses of calcitriol could be appropriately treated with low doses of falecalcitriol.\n                  <\/jats:p>","DOI":"10.1530\/jme-16-0048","type":"journal-article","created":{"date-parts":[[2016,5,7]],"date-time":"2016-05-07T09:31:51Z","timestamp":1462613511000},"page":"23-32","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":3,"title":["Transcriptional activation of the wild-type and mutant vitamin D receptors by vitamin D3 analogs"],"prefix":"10.1530","volume":"57","author":[{"given":"Kumi","family":"Futawaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tetsuya","family":"Tagami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Koyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Nushida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoko","family":"Nezu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hironori","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyuki","family":"Imamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Kasahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Moriyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"2016062919131286000_57.1.23.1","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-012-0098-z"},{"key":"2016062919131286000_57.1.23.2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(88)90177-3"},{"key":"2016062919131286000_57.1.23.3","doi-asserted-by":"publisher","DOI":"10.2165\/00024677-200201050-00004"},{"key":"2016062919131286000_57.1.23.4","doi-asserted-by":"crossref","unstructured":"Carlberg C 2014 Genome-wide (over)view on the actions of vitamin D. 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