Project/Area Number |
15K11433
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Social dentistry
|
Research Institution | Kanagawa Dental College |
Principal Investigator |
|
Co-Investigator(Kenkyū-buntansha) |
Bhawal Ujjal 日本大学, 松戸歯学部, 助教 (50433339)
|
Project Period (FY) |
2015-04-01 – 2019-03-31
|
Project Status |
Completed (Fiscal Year 2018)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
Keywords | 低濃度フッ化物 / 老化 / 転写因子 / 加齢 / DNAマイクロアレイ / microRNAマイクロアレイ / 寿命制御 / 老化・寿命 / 角化歯肉上皮細胞 |
Outline of Final Research Achievements |
In this study, we developed genome-wide screening of NaF induced senescent cell master transcription factor (Dec1: Differentiated Embryo Chondrocyte 1) to clarify the regulation of target genes and the control mechanism of senescent cells using DEC1 KO mice. We evaluated the influence of DEC1 gene on bone tissue to elucidate physiological function of senescent cells in term of bone metabolism and autoimmunity. Total RNA was isolated from femoral tissue of 3-month-old and 24-month-old WT and Dec1 Knockout (KO) mice. Their gene expression and miRNA expression findings were analyzed using DNA microarrays and miRNA arrays in combination with GeneSpring and Ingenuity Pathways Analysis. Gene ontology (GO) analysis revealed that it incorporates critical transcription-related processes and intracellular signaling of genes targeted to miRNA. Several signaling pathways, such as cAMP-mediated signal, tight junction signal, and gap junction signal are involved in bone senescence.
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Academic Significance and Societal Importance of the Research Achievements |
フッ化物は骨や歯質など硬組織への影響は以前から報告されているが、申請者はNHOKがフッ化物を作用させることで増殖すること、また、ラットにおいても皮膚創傷実験において線維芽細胞増殖因子FGF2, FGF7の発現が上昇し、歯周組織のアンチエイジングのみならず、皮膚をはじめ全身のアンチエイジングの創薬へと繋がる可能性があると考えたことと、老化細胞マスター転写因子 (DEC1: Differentiated Embryo Chondrocyte 1) KOマウスを用い、フッ化物投与がどのような影響があるかを明らかにしていくところから、先進的で独創的な結果が期待された。
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