Regulation of bone metabolism by circadian clock system

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461558
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Research Institute, Osaka Medical Center for Maternal and Child Health
• Principal Investigator: Kawai Masanobu (カワイマサノブ) 地方独立行政法人大阪府立病院機構大阪府立母子保健総合医療センター(研究所), 環境影響部門, 主任研究員 (50598117)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 生物時計 / Bmal1 / VDR / カルシウム

Outline of Final Research Achievements

The effects of circadian clock system in the regulatin of bone metabolism was investigated using mice lacking Bmal1, a core clock gene, in the intestine (cKO mice). cKO mice displayed impaired Calcium (Ca) absorption associated with elevations in PTH levels. Mechanistically, VDR showed rhythmic transcriptional pattern in the intestine, and this was dissapeared in cKO mice. Skeletal phentyping of cKO mice revealed decreases in bone mass associated with enhanced bone resorption. additionally, decreased bone mass was not observed when mice were fed with high Ca diet. Collectively, these findings suggest that circadian clock system in the intestine regulates bone metabolism by fine-tuning Ca absorption.

Free Research Field

小児内分泌学