| Project/Area Number |
16H05327
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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 |
Metabolomics
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| Research Institution | The University of Tokushima |
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Principal Investigator |
MATSUMOTO Toshio 徳島大学, 先端酵素学研究所(オープンイノベ), 名誉教授 (20157374)
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| Co-Investigator(Kenkyū-buntansha) |
福本 誠二 徳島大学, 先端酵素学研究所(オープンイノベ), 特任教授 (30202287)
沢津橋 俊 徳島大学, 先端酵素学研究所(オープンイノベ), 特任講師 (70535103)
MARIA TSOUMPRA 徳島大学, 先端酵素学研究所(オープンイノベ), 特任研究員 (80756198)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 遺伝子 / シグナル伝達 / 脂質 / 老化 / 骨粗鬆症 / 骨代謝 / 骨・カルシウム代謝異常 / 骨代謝学 / 骨ー脂肪組織関連 / 骨－脂肪組織連関 |
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| Outline of Final Research Achievements |
Interleukin (IL)-11 enhances osteogenesis and suppresses adipogenesis from bone marrow stromal cells, by enhancing Wnt signaling via suppression of Wnt inhibitors. To clarify the role of IL-11 in bone remodeling, IL-11 knockout (IL-11-/-) mice were created. IL-11-/- mice exhibited reduced bone formation with suppressed Wnt signaling via enhanced expression of Wnt inhibitors. These mice showed not only reduced bone mass but also increased white adipose tissue with glucose intolerance. Osteoblast-specific IL-11 deletion in osteocalcin-Cre;IL-11fl/fl mice showed reduced serum IL-11 level and almost the same phenotype as IL-11-/- mice. Adipocyte-specific IL-11 deletion in adiponectin-Cre; IL-11fl/fl mice exhibited no abnormality. Thus, osteoblast-derived IL-11 controls not only osteogenesis but also systemic adipogenesis and energy metabolism. Receptors and intracellular signaling mediating these effects of IL-11 are currently under investigation.
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| Academic Significance and Societal Importance of the Research Achievements |
骨由来のIL-11が古典的Wntシグナル抑制因子の発現制御を介し、骨髄前駆細胞からの骨芽細胞・脂肪細胞の分化スイッチによる骨形成の促進のみならず、全身脂肪組織にも影響を及ぼし、エネルギー代謝をも制御することが示された。本研究によりオステオカルシンに加え新たに骨と脂肪組織・エネルギー代謝とのIL-11を介する密接な連関が明らかとなり、IL-11シグナルの制御を介する骨粗鬆症およびメタボリック症候群に対する新たな予防・治療法の開発に向けたアプローチに繋がるものと期待される。
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