Generation of 1,25-dihydroxyvitamin D 3 in Cyp27b1 knockout mice by treatment with 25-hydroxyvitamin D 3 rescued their rachitic phenotypes

Miyu Nishikawa, Kaori Yasuda, Masashi Takamatsu, Keisuke Abe, Kimie Nakagawa, Naoko Tsugawa, Yoshihisa Hirota, Kazuma Tanaka, Shigeaki Yamashita, Shinichi Ikushiro, Tatsuo Suda, Toshio Okano, Toshiyuki Sakaki

研究成果: Article査読

10 被引用数 (Scopus)


We have reported that 25-hydroxyvitamin D 3 [25(OH)D 3 ] binds to vitamin D receptor and exhibits several biological functions directly in vitro. To evaluate the direct effect of 25(OH)D 3 in vivo, we used Cyp27b1 knockout (KO) mice, which had no detectable plasma 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] when fed a diet containing normal Ca and vitamin D. Daily treatment with 25(OH)D 3 at 250 μg kg -1 day -1 rescued rachitic phenotypes in the Cyp27b1 KO mice. Bone mineral density, female sexual cycles, and plasma levels of Ca, P, and PTH were all normalized following 25(OH)D 3 administration. An elevated Cyp24a1 mRNA expression was observed in the kidneys, and plasma concentrations of Cyp24a1-dependent metabolites of 25(OH)D 3 were increased. To our surprise, 1,25(OH) 2 D 3 was detected at a normal level in the plasma of Cyp27b1 KO mice. The F1 to F4 generations of Cyp27b1 KO mice fed 25(OH)D 3 showed normal growth, normal plasma levels of Ca, P, and parathyroid hormone, and normal bone mineral density. The curative effect of 25(OH)D 3 was considered to depend on the de novo synthesis of 1,25(OH) 2 D 3 in the Cyp27b1 KO mice. This suggests that another enzyme than Cyp27b1 is present for the 1,25(OH) 2 D 3 synthesis. Interestingly, the liver mitochondrial fraction prepared from Cyp27b1 KO mice converted 25(OH)D 3 to 1,25(OH) 2 D 3 . The most probable candidate is Cyp27a1. Our findings suggest that 25(OH)D 3 may be useful for the treatment and prevention of osteoporosis for patients with chronic kidney disease.

ジャーナルJournal of Steroid Biochemistry and Molecular Biology
出版ステータスPublished - 2019 1

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 分子医療
  • 分子生物学
  • 内分泌学
  • 臨床生化学
  • 細胞生物学


「Generation of 1,25-dihydroxyvitamin D <sub>3</sub> in Cyp27b1 knockout mice by treatment with 25-hydroxyvitamin D <sub>3</sub> rescued their rachitic phenotypes」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。