| Project/Area Number |
17591551
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MATSUDAIRA Ko The University of Tokyo, Faculty of Medicine, Assistant Professor (10302697)
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| Co-Investigator(Kenkyū-buntansha) |
OGATA Naoshi The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor (10361495)
IKEDA Tosiyuki The University of Tokyo, Faculty of Medicine, Visiting Assistant Professor (80322759)
MATSUBARA Takehiro The University of Tokyo, Faculty of Medicine, Intern Doctor (40361498)
川口 浩 東京大学, 医学部附属病院, 助教授 (40282660)
中村 耕三 東京大学, 医学部附属病院, 教授 (60126133)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Adiponectin / bone / lipid / osteoporosis / 骨形成 / ノックアウトマウス / トランスジェニックマウス |
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| Research Abstract |
Since interaction between bone and lipid metabolism has been suggested, this study investigated the regulation of bone metabolism by adiponectin, a representative adipokine, by analyzing deficient and overexpressing transgenic mice. Weinitially confirmed that adiponectin and its receptors were expressed in osteoblastic and osteoclastic cells, indicating that adiponectin can act on bone not only through an endocrine pathway as a hormone secreted from fat tissue, but also through an autocrine/paracrine pathway. There was no abnormality in bone mass or turnover of adiponectin-deficient (Ad_/_) mice, possibly due to an equivalent balance of the two pathways. In the culture of bone marrow cells from the Ad_/_mice, osteogenesis was decreased compared to the wild-type (WT) cell culture, indicating a positive effect of endogenous adiponectin through the autocrine/paracrine pathway. To examine the endocrine action of adiponectin, we analyzed transgenic mice overexpressing adiponectin in the liver, and found no abnormality in the bone. Addition of recombinant adiponectin in cultured osteoprogenitor cells suppressed osteogenesis, suggesting that the direct action of circulating adiponectin was negative for bone formation. In the presence of insulin, however, this suppression was blunted, and adiponectin enhanced the insulin-induced phosphorylations of the main downstream molecule insulin receptor substrate-1 and Akt. These lines of results suggest three distinct adiponectin actions on bone formation: a positive action through the autocrine/paracrine pathway by locally produced adiponectin, a negative action through the direct pathway by circulating adiponectin, and a positive action through the indirect pathway by circulating adiponectin via enhancement of the insulin signaling.
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