| Project/Area Number |
23KF0016
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund |
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| Section | 外国 |
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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2023-04-25 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2024: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2023: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Bone dysmetabolism / Alzheimer’s disease / Ageing / Cognitive decline |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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