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Role of low-level fluoride in aging and its underlying cellular mechanisms

Research Project

Project/Area Number 15K11433
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Social dentistry
Research InstitutionKanagawa Dental College

Principal Investigator

Arakawa Hirohisa  神奈川歯科大学, 歯学部, 特任教授 (00130906)

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.

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。

Report

(5 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (12 results)

All 2019 2018 2017 2016 2015

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (9 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] The Role of Low-Level Sodium Fluoride in Periodontal Inflammation2019

    • Author(s)
      Il-Shin Kim, Wenqun Song, Hirohisa Arakawa
    • Journal Title

      Journal of Hard Tissue Biology

      Volume: 28 Issue: 2 Pages: 159-164

    • DOI

      10.2485/jhtb.28.159

    • NAID

      130007636418

    • ISSN
      1341-7649, 1880-828X
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] フッ化物の新たな視点-歯周病予防に関する研究の進展-2017

    • Author(s)
      Ujjal K.Bhawal、吉田清美、荒川浩久
    • Journal Title

      歯界展望

      Volume: 130 Pages: 1031-1034

    • Related Report
      2017 Research-status Report
  • [Journal Article] Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss2015

    • Author(s)
      Bhawal UK, Lee HJ, Arikawa K, Shimosaka M, Suzuki M, Toyama T, Sato T, Kawamata R, Taguchi C, Hamada N, Nasu I, Arakawa H, Shibutani K
    • Journal Title

      International Journal of Oral Science

      Volume: 7(4) Issue: 4 Pages: 242-249

    • DOI

      10.1038/ijos.2015.28

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Insights into the mechanisms of low-level fluoride in preventing periodontal disease: current status and future expectations2018

    • Author(s)
      Ujjal K. Bhawal, Yu Fujita, Ikuo Nasu, Hirohisa Arakawa
    • Organizer
      13th International Conference of the Asian Academy of Preventive Dentistry
    • Related Report
      2018 Annual Research Report
  • [Presentation] Role of stromal cell-derived factor 1 alpha and CXCR4 in Porphyromonas gingivalis-induced periodontal inflammation2018

    • Author(s)
      Fengzhu Zhang, Ujjal K. Bhawal, Chieko Taguchi, Kazumune Arikawa, Ikuo Nasu, Hirohisa Arakawa, Koh Shibutani
    • Organizer
      第67回日本口腔衛生学会・総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss2017

    • Author(s)
      Bhawal UK, Suzuki M, Arakawa H, Shibutani K, Nasu I, Hiratsuka K
    • Organizer
      95th General Session & Exhibition of the IADR
    • Place of Presentation
      San Francisco, California, USA
    • Year and Date
      2017-03-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Micromolar levels of sodium fluoride promote osteoblast differentiation through Runx2 signaling2017

    • Author(s)
      Bhawal UK, Arikawa K, Taguchi C, Uchiyama T, Hiratsuka K, Arakawa H, Nasu I
    • Organizer
      第66回日本口腔衛生学会・総会
    • Related Report
      2017 Research-status Report
  • [Presentation] The effects of low-power laser irradiation in submandibular glands of diabetes-induced rats2017

    • Author(s)
      Bhawal UK, Uchiyama T, Arikawa K, Oka S, Hiratsuka K, Arakawa H, Nasu I, Shibutani K
    • Organizer
      IUPS 38th World Congress
    • Related Report
      2017 Research-status Report
  • [Presentation] Differentiated embryo chondrocyte 1 (DEC1) is a novel negative regulator of hepatic fibroblast growth factor 21 (FGF21) in aging mice2016

    • Author(s)
      Bhawal UK, Arikawa K, Taguchi C, Nakayama R, Nasu I, Arakawa H, Hiratsuka K
    • Organizer
      第65回日本口腔衛生学会・総会; The 12th International Conference of Asian Academy of Preventive Dentistry : AAPD
    • Place of Presentation
      東京医科歯科大学 M&Dタワー 鈴木章夫記念講堂、東京、東京
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] MicroRNA expression profiling and inhibition of inflammation of Korean red ginseng extract in rats on kanamycin-induced hearing loss2016

    • Author(s)
      Bhawal UK, Arikawa K, Taguchi C, Nakayama R, Nasu I, Arakawa H, Hiratsuka K
    • Organizer
      第65回日本口腔衛生学会・総会; The 12th International Conference of Asian Academy of Preventive Dentistry : AAPD
    • Place of Presentation
      東京医科歯科大学 M&Dタワー 鈴木章夫記念講堂、東京、東京
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] DNA microarray and MicroRNA analysis in low-level laser therapy (LLLT)-treated diabetic rat salivary glands2016

    • Author(s)
      Bhawal UK, Arikawa K, Taguchi C, Nakayama R, Nasu I, Arakawa H, Hiratsuka K
    • Organizer
      第65回日本口腔衛生学会・総会; The 12th International Conference of Asian Academy of Preventive Dentistry : AAPD
    • Place of Presentation
      東京医科歯科大学 M&Dタワー 鈴木章夫記念講堂、東京、東京
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] Micromolar sodium fluoride mediates anti-osteoclastogenesis in Porphyromonas gingivalis-induced alveolar bone loss.2015

    • Author(s)
      Bhawal UK, Arikawa K, Hamada N, Nasu I, Hiratsuka K, Arakawa H
    • Organizer
      2015 FDI Annual World Dental Congress
    • Place of Presentation
      Bangkok, Thailand
    • Year and Date
      2015-09-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2020-03-30  

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