Low Level Fluoride Stimulates Epithelial-Mesenchymal Interaction in Oral Mucosa

  • He Dawei
    Department of Health Science, Division of Oral Health, Kanagawa Dental College
  • Ujjal K. Bhawal
    Department of Health Science, Division of Oral Health, Kanagawa Dental College Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo
  • Hamada Nobushiro
    Department of Infection Control, Division of Microbiology, Kanagawa Dental College
  • Kuboyama Noboru
    Department of Oral Molecular Pharmacology, Nihon University School of Dentistry at Matsudo
  • Abiko Yoshimitsu
    Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo
  • Arakawa Hirohisa
    Department of Health Science, Division of Oral Health, Kanagawa Dental College

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Oral mucosa consists of the superficial epithelium and the underlying lamina propria, and it functions as a barrier against exogenous substances. In development, interactions of stem/progenitor cells of the epithelium and mesenchyme are crucial to the morphogenesis of oral mucosa. Our previous work in low level fluoride-induced cell motility of epithelial cells has yielded important clues for periodontal physiology. This study focuses on a working concept of low level fluoride to provide a conducive oral environment for pivotal epithelial-mesenchymal interactions. Cultured human primary gingival epithelial cells treated with 50 μM NaF were investigated by DNA microarray. Quantitative real-time PCR and an in vivo experimental rat skin wound model were employed to confirm the findings obtained with the microarray analysis. Microarray data revealed that low level fluoride-treated human gingival epithelial cells elevated various biological processes. The key proliferation markers, FGF2 and FGF7, and mesenchymal marker, Twist1, expression was up-regulated and quantitative real-time PCR confirmed this observation. Our in vivo study revealed that low concentration of NaF increased FGF2, FGF7, and Twist1 protein expression in fluoride-treated skin wound tissues compared with controls. These results provide new information on low level fluoride-induced epithelial-mesenchymal interactions and may thus aid in the understanding of oral mucosa development.

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