| Project/Area Number |
16K11476
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Okayama University |
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Principal Investigator |
Hattori Takako 岡山大学, 医歯薬学総合研究科, 助教 (00228488)
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| Co-Investigator(Kenkyū-buntansha) |
久保田 聡 岡山大学, 医歯薬学総合研究科, 教授 (90221936)
西田 崇 岡山大学, 医歯薬学総合研究科, 准教授 (30322233)
高江洲 かずみ (河田かずみ) 岡山大学, 医歯薬学総合研究科, 助教 (10457228)
池亀 美華 岡山大学, 医歯薬学総合研究科, 准教授 (70282986)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | メラトニン / AANAT / 概日リズム / 軟骨細胞 / メラトニン受容体 / BMAL1 / PER1 / 骨格成長 / 細胞増殖 / mass spectrometry / Bmal1 / chondrocytes / melatonin / rhythmic expression / PTHrP / IHH / Cell growth / circadian rhythm / cell growth / 軟骨組織 / 成長 / 内軟骨性骨形成 |
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| Outline of Final Research Achievements |
1. Gene expression of melatonin-synthesizing enzymes and melatonin receptors wes detected in mouse primary chondrocytes. 2. Production of melatonin in chondrocytes was confirmed by mass spectrophotometric analysis. 3. Melatonin enhanced chondrocyte growth and increased expression of chondrocyte markers, but inhibited hypertrophy. These effects was abolished by addition of an antagonist. 4. Melatonin rapidly upregulaed a melatonin synthesizing enzyme and receptor expression and expression of the clock gene Bmal1, while downregulated Per1. 5. Chronobiological analysis of C3H mouse chondrocytes, which express melatonin, revealed that melatonin induced the cyclic expression of melatonin and modified the cyclic rhythm of Bmal1, Mt1 and Mt2, but not in BALB/c mouse chondrocytes. These results indicate that exogenous and endogenous melatonin works in synergy in chondrocytes to adjust rhythmic expression to the central suprachiasmatic nucleus clock.
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| Academic Significance and Societal Importance of the Research Achievements |
網膜からの光刺激を受けて松果体より概日リズムを示しながら合成、分泌されるメラトニンが、軟骨細胞自身の概日リズムを持ったメラトニン合成を誘導し、その合成されたメラトニンが軟骨細胞における概日リズムを中枢のリズムと同調させ、軟骨細胞の増殖促進、肥大化抑制、軟骨基質の合成促進を行うことを明らかにした。「寝る子は育つ」とは、夜間にメラトニンが内軟骨性骨形成を促進することを示す最初の報告である。
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