| Project/Area Number |
17K18417
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Eating habits
Embryonic/Neonatal medicine
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
Yasunaga Mayu 国立研究開発法人産業技術総合研究所, 生命工学領域, 研究員 (70712181)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 低栄養 / 骨形成 / オステオカルシン / 間葉系幹細胞 / グルコース / 骨芽細胞 / MSC / 胎児期低栄養 / 骨形成不良 / 2型糖尿病 / 遺伝子発現 / エピジェネティックな発現制御 |
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| Outline of Final Research Achievements |
To investigate the mechanism involved in type II diabetes induced by the mother’s undernutrition during pregnancy, we developed an in vitro model that rat mesenchymal stem cells (MSCs) were induced osteogenic differentiation at a high and low glucose concentration in osteogenesis induction medium, and verified that impacts on cell differentiation, proliferation and function.
Low glucose decreased osteogenesis differentiation markers, including ALP activity and carboxylated osteocalcin secretion as well as proliferation. Uncarboxylated osteocalcin, which is specifically expressed in osteoblasts and secreted into the circulation, regulates glucose homeostasis by stimulating insulin expression in pancreas, was secreted according to the differentiation mature level of osteoblasts similar to carboxylated osteocalcin. Thus, these results indicate that nutrition change in the osteogenesis differentiation process could impact cell differentiation, proliferation and function.
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| Academic Significance and Societal Importance of the Research Achievements |
間葉系幹細胞の骨分化誘導を用いた当該現象のin vitro低栄養モデルの構築に成功したことは劇的な変化を生じる発生期での複雑な疾患素因の形成メカニズムの解明に大きく寄与すると考えられる。さらに膵臓β細胞の増殖や機能に関わるGlu型オステオカルシンは骨分化度に応じて変化する可能性が示唆され、本研究のコンセプトである骨形成不良による膵臓β細胞の発生・機能への影響について支持するデータの一つとなった。本研究により未だ全く不明の「低体重で生まれた人で成人期に罹患しやすいII型糖尿病の発症機構」の一端が明らかとなり、発症機構の全体像解明への重要な基礎的知見が得られた。
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