| 研究課題/領域番号 |
23KF0016
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 |
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| 応募区分 | 外国 |
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| 審査区分 |
小区分56020:整形外科学関連
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| 研究機関 | 東京大学 |
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研究代表者 |
高柳 広 東京大学, 大学院医学系研究科(医学部), 教授 (20334229)
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| 研究分担者 |
SHI TIANSHU 東京大学, 大学院医学系研究科(医学部), 外国人特別研究員
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| 研究期間 (年度) |
2023-04-25 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
2,400千円 (直接経費: 2,400千円)
2024年度: 1,200千円 (直接経費: 1,200千円)
2023年度: 1,200千円 (直接経費: 1,200千円)
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| キーワード | Bone dysmetabolism / Alzheimer’s disease / Ageing / Cognitive decline |
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| 研究開始時の研究の概要 |
Bone functions as an endocrine organ secreted “osteokines” to regulate the homestasis of extraosseous organs under pathological conditions. Although osteoporosis patients exhibited a higher risk of Alzheimer's disease (AD), the explicit mechanism of bone-brain axial regulation was elusive. Here, we aim to demonstrate the existence of bone-immunology-brain systems which may be involved in the AD progress, which paved a brand-new way for therapeutic intervention in AD patients with several osteoporosis.
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| 研究実績の概要 |
We revealed the connection between bone dysmetabolism and cognitive impairment. Emerging evidence reports bone dysmetabolism could increase the risk of dementia, especially Alzheimer’s disease (AD). Our research showed that the serum level of osteocyte-derived sclerostin was positively associated with cognitive impairment in elderly individuals and aged mice. gain-of and loss-of-function of mice indicated osteocyte-derived sclerostin could pass through the blood-brain barrier (BBB) in aged mice to accelerate the cognitive impairment through the Lrp6/β-catenin/BACE1 pathway. Targeted decreasing the osteocyte-derived sclerostin not only improves bone formation but also alleviates cognitive decline in Alzheimer’s disease, which suggests a mutual therapeutic effect on bone and brain during AD progress. This paper has been published in Nature Metabolism (DOI:10.1038/s42255-024-00989-x).
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
This paper has been published in Nature Metabolism, named as ‘Osteocyte-derived sclerostin impairs cognitive function during aging and Alzheimer’s disease progression’.Our paper has been invited to write the Research Briefing and one of my pictures in the main figures has been chosen to be the Cover Image, which was published with the paper and Research Briefing in the same volume (Volume 6 Issue 3, March 2024).
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| 今後の研究の推進方策 |
We continue to analyze other bone-derived factors (osteokines) that may play an important role in cognitive function during bone dysmetabolism. Additionally, our research on osteoimmunology suggests that bone dysmetabolism may regulate the immune system, including the T cells, B cells, etc during aging, which may further impact brain function. Thus, we plan to analyze the changes in the immune system during aging or pathogenesis conditions, which may provide a new pathway for connection the between bone dysmetabolism and cognitive decline.
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