| Project/Area Number |
26861549
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Ehime University |
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Principal Investigator |
Lee Ji-Won 愛媛大学, プロテオサイエンスセンター, 助教(特命教員) (70711274)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | osteoclast / chemokine / CCR5 / RANKL / cytoskeleton / bone / small GTPase |
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| Outline of Final Research Achievements |
- Physiological roles of CCR5 in bone metabolism; Ccr5-deficient mice had significantly increased number and size of osteoclasts, although they did not show significant difference in BMD compared to their wild-type littermates. In keeping with osteoclast dysfuction, Ccr5-deficient mice were less susceptible to RANKL-induced bone loss, reflecting functional impairment of osteoclasts.
- Elucidation of signaling pathway in Ccr5-/- mice; Ccr5-deficient osteoclasts showed decreased bone resorption activity accompanied with impaired and disorganized adhesive structures, demonstrated using confocal and super-resolution microscopy. Our molecular results suggested that CCR5-mediated signal was involved in integrin-mediated small GTPase activation that was required for proper osteoclasts function. Our findings unveil unique and essential roles of CCR5 in bone metabolism and bone destruction diseases, and have implications concerning bone physiopathology for the HIV therapy targeting CCR5.
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