2016 Fiscal Year Final Research Report
Maintenance of bone homeostasis by DLL1-mediated Notch activation
| Project/Area Number |
26430094
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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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| Research Field |
Laboratory animal science
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| Research Institution | Tokai University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | Notchシグナル / 骨代謝 / 骨芽細胞 / リガンド特異性 |
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| Outline of Final Research Achievements |
By using a transgenic approach that modified the expression of delta-like 1 (DLL-1) or Jagged1 in osteoblast-specific manner, we investigated the ligand-specific effects of Notch signaling in bone homeostasis. We demonstrated that the proper regulation of DLL1 expression in osteoblasts was essential for maintenance of bone remodeling. DLL1-Notch signaling promoted proliferation of committed but immature osteoblasts, thus being responsible for the expansion of bone forming cell pool. However, DLL1-Notch signaling inhibited further differentiation of those expanded osteoblasts to become fully mature functional osteoblasts, causing a substantial decrease in bone formation. Although osteoblast-specific expression of DLL1 did not alter intrinsic ability of osteoclasts, deregulation of osteoblast differentiation and maturation impaired maturation and function of osteoclasts due to a failed osteoblast-osteoclast coupling, resulting in severely suppressed bone metabolic turn-over.
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| Free Research Field |
幹細胞生物学
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