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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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000)
Fiscal Year 2012: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2011: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2010: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Keywords | 分子病退学 / RANKL / 骨代謝 / 遺伝子 / 細胞・組織 / 生体分子 / 発生・分化 / 老化 |
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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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Report
(4 results)
Research Products
(35 results)
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[Journal Article] Histological examination on osteoblastic activities in the alveolar bone of transgenic mice with induced ablation of osteocytes2013
Author(s)
Li M, Hasegawa T, Hogo H, Tatsumi S, Liu Z, Guo Y, Sasaki M, Tabata C, Yamamoto T, Ikeda K, Amizuka N
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Journal Title
Histol Histopathol
Volume: 28
Pages: 327-335
Related Report
Peer Reviewed
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[Journal Article] SIRT1 Regulates Thyroid-Stimulating Hormone Release by Enhancing PIP5Kγ Activity through Deacetylation of Specific Lysine Residues in Mammals2010
Author(s)
Akieda-Asai S, Zaima N, Ikegami K, Kahyo T, Yao I, Hatanaka T, Iemura S-i, Sugiyama R, Yokozeki T, Eishi Y, Koike M, Ikeda K, Chiba T, Yamaza H, Shimokawa I, Song Si-Y, Matsuno A, Mizutani A, Sawabe M, Chao MV, Tanaka M, Kanaho Y, Natsume T, Sugimura H, Date Y, McBurney MW, Guarente L, Setou M
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Journal Title
PLoS ONE
Volume: 5
Pages: 11755-11755
Related Report
Peer Reviewed
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[Presentation] 鉄と破骨細胞2010
Author(s)
池田恭治
Organizer
第34回日本鉄バイオサイエンス学会
Place of Presentation
東京
Year and Date
2010-09-12
Related Report
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