Investigation of chromatic remodeling in osteoclast function for therapeutic targeting of bone remodeling balance
| Project/Area Number |
19K10044
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57010:Oral biological science-related
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| Research Institution | Hokkaido University (2021-2022)
Ehime University (2019) |
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Principal Investigator |
Lee Ji-Won 北海道大学, 歯学研究院, 助教 (70711274)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | chromatin remodeler / BAF155 / osteoclast / bone / Osteoclast / Baf155 / Chromatin remodeler / sexual dimorphism / Bone / SWI/SNF / Histomorphometry / Rank / Lysosome |
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| Outline of Research at the Start |
Our current observation on CCR5 as a co-receptor of HIV, firstly shows functionally distinctive bone phenotype, and suggest ‘Drug-repositioning’ effect of CCR5-targeted therapy, indicating not only HIV blocker but also protector against bone-destructive conditions. In our ongoing experiments, we have identified CCR5-mediated protein targets of BAF complex that may affect to osteoclast function. In here, we will seek for the mechanisms of chromatin remodeling complex mediating regulation of osteoclast function for anabolic bone remodeling by taking genome-wide approaches.
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| Outline of Final Research Achievements |
This study investigated the functional role of Baf155, an epigenetic chromatin remodeler in osteoclasts. In this fiscal year, we found that the effect of Baf155 cKO mice on bone mineral density (BMD) differed between sexes, even at the same age. Interestingly, microCT analysis of 8-week-old mice showed an increase in BMD only in male mice, but there was no difference in BMD at 16 weeks of age. Conversely, in 8-week-old female mice, there was no difference in BMD compared to the control group, but at 16 weeks of age, BMD parameter significantly increased in Baaf155 cKO. Our results suggest that the epigenetic regulation of the chromatin regulator Baf155 on osteoclasts and bone differs according to sexual dimorphism.
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| Academic Significance and Societal Importance of the Research Achievements |
Age-related bone resorption diseases are common in women. However, there are no gender-specific clinical trials or drug guidelines. From a gender difference medical perspective, the accumulation of pathophysiological evidence is important.
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Report
(4 results)
Research Products
(10 results)
