Mechanistic analysis of menopause-induced bone mineral density loss focussing on colonic epithelial homeostasis

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K17677
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition
• Principal Investigator: Kondo Takashi 国立研究開発法人医薬基盤・健康・栄養研究所, 国立健康・栄養研究所 食品保健機能研究部, 研究員 (30832307)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 骨代謝 / 閉経後骨粗鬆症

Outline of Final Research Achievements

The mechanism of menopause-induced reduction in bone mineral density has been explained solely from the lack of estrogen. In the present study, we tested whether the lack of estrogen disrupt colonic homeostasis and whether colon-derived inflammatory substances induce the reduction in bone mineral density. The cecal mucin and the concentration of LPS-binding protein in the blood did not change in normal female mice and ovariectomized mice, indicating that the lack of estrogen does not affect the barrier function of the large intestine. On the other hand, the RNA sequences of comprehensive analysis of bone marrow genes found that the lack of estrogen suppressed the ferotosis pathway. This finding may explain the mechanism of action of anti-inflammatory components in reducing bone mineral density.

Free Research Field

栄養生理

Academic Significance and Societal Importance of the Research Achievements

閉経により生じる疾患は女性のキャリア形成に限らず、生活の質を著しく低下させる。女性ホルモンの分泌停止が大腸のバリア機能に影響しないという知見は骨密度低下の主要因とされる炎症が何に由来するのかを探索手掛かりになる。また、骨密度低下とフェロトーシスの関連性は、これまでに存在しない副作用のない閉経後骨粗鬆症予防食品を開発するきっかけとなる。