Biological functions and mechanisms of unliganded VDR on bone and calcium metabolism.

• Project/Area Number: 24614004
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrated Nutrition Science
• Research Institution: The University of Tokyo
• Principal Investigator: YAMAMOTO Yoko 東京大学, 医学部附属病院, 助教 (30376644)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: ビタミンD / ビタミンD受容体 / カルシウム代謝 / 骨代謝 / 遺伝子改変マウス / VDR / 栄養化学 / 骨芽細胞 / 破骨細胞

Outline of Final Research Achievements

Vitamin D is a primary regulator in many biological phenomena such as calcium homeostasis and bone formation. Such actions are thought to be mediated through transcriptional controls by the vitamin D receptor (VDR). Ligand-induced function of VDR have been well established, however, the physiological impact of unliganded VDR still remains unclear. Here we report that VDR helix 12 deletion (ΔAF2) mutant mice fed with high calcium diet exhibited impaired bone formation unlike VDRKO mice. Trabeculae in VDRΔAF2 mice were filled with fibroblast-like cells instead of bone marrow. Microarray and real-time RT-PCR analyses of kidney in VDRKO and VDRΔAF2 mice reveal distinct gene expression profiles. Six putative target genes regulated by unliganded VDR and responsible for impaired bone formation were identified.

Research Products

• [Journal Article] Vitamin D receptor in osteoblasts is a negative regulator of bone mass control (2013)
  • Author(s): Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Naka michi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y.
  • Journal Title: Endocrinology. Volume: 154 Issue: 3 Pages: 1008-20
  • DOI: 10.1210/en.2012-1542
  • Peer Reviewed