2012 Fiscal Year Final Research Report
Physiologic functions of RANKL in bone metabolism
| Project/Area Number |
22390064
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | National Center for Geriatrics and Gerontology |
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Principal Investigator |
IKEDA Kyoji 独立行政法人国立長寿医療研究センター, 運動器疾患研究部, 部長 (00222878)
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| Co-Investigator(Renkei-kenkyūsha) |
FUMOTO Toshio (独)国立長寿医療研究センター, 運動器疾患研究部, 研究員 (80463206)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 分子病退学 |
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| Research Abstract |
The cytokine RANKL is essential for osteoclast development in bone. The cellular sources of RANKL for support of osteoclast generation under various pathophysiological conditions have remained unclear, however. In this study we have shown that inactivation of Rankl specifically in osteoblast lineage cells with the use of an Osterix-Cre transgene results in typical osteopetrosis in the trabecular compartment of the tibia, with the phenotype being much less marked in the vertebrae. In contrast to its effects on trabecular bone, osteoblastic deficiency of RANKL resulted in thinning of the femoral cortex in association with suppression of bone formation during the modeling process. Ablation of RANKL specifically in T cells resulted in a moderate but significant increase in tibial trabecular bone. Mice with osteoblastic deficiency of RANKL were protected from bone loss induced by ovariectomy and also from joint destruction associated with arthritis, whereas loss of RANKL in T cells did not confer such protection. Finally, inducible deletion of Rankl selectively in the osteoblasts at 6 wk of age resulted in an increase in bone mass in association with reduced bone resorption and formation at 12 wk. Our results thus suggest that RANKL produced by osteoblasts contributes to osteoclast development in vivo.
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Research Products
(12 results)
