Fluoride reduces the expression of enamel proteins and cytokines in an ameloblast-derived cell line

Arch Oral Biol. 2011 Apr;56(4):324-30. doi: 10.1016/j.archoralbio.2010.10.024. Epub 2010 Dec 17.


Objective: To investigate the effects of two different fluoride concentrations on the expression of enamel proteins, alkaline phosphatase (ALP), cytokines and interleukins by an ameloblast-derived cell line.

Methods: Murine ameloblast-derived cells (LS-8), mouse odontogenic epithelia, were exposed to 1 or 5ppm sodium fluoride (NaF) (0.46 and 2.25ppm F, respectively) for 1, 3 and 7 days. The effect of NaF on the mRNA expression of enamel proteins was quantified; the secretion of cytokines, and interleukins, and the alkaline phosphatase (ALP) activity, into the cell culture medium was measured and compared to untreated controls. The effect on cell growth after 1- and 3-days in culture was measured using BrdU incorporation.

Results: Fluoride at 2.25ppm reduced mRNA expression of the structural enamel matrix proteins amelogenin (amel), ameloblastin (ambn), enamelin (enam), and the enamel protease matrix metallopeptidase-20 (MMP-20). Similarly several vascularisation factors (vascular endothelial growth factor (VEGF), monocyte chemoattractant proteins (MCP-1) and interferon inducible protein 10 (IP-10), was also reduced by 2.25ppm fluoride. ALP activity and proliferation were stimulated by 0.46ppm fluoride but inhibited by 2.25ppm fluoride.

Conclusions: These results indicate that fluoride may impact on the expression of structural enamel proteins and the protease responsible for processing these proteins during the secretory stage of amelogenesis and go some way to explaining the mineralization defect that characterises fluorotic enamel.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / drug effects
  • Alkaline Phosphatase / metabolism
  • Ameloblasts / cytology
  • Ameloblasts / drug effects*
  • Ameloblasts / metabolism
  • Animals
  • Calcium / metabolism
  • Cariostatic Agents / pharmacology*
  • Cell Line
  • Cell Proliferation / drug effects*
  • Cytokines / drug effects
  • Cytokines / metabolism
  • Dental Enamel Proteins / drug effects*
  • Dental Enamel Proteins / metabolism
  • Dose-Response Relationship, Drug
  • Interleukins / metabolism
  • L-Lactate Dehydrogenase / drug effects
  • L-Lactate Dehydrogenase / metabolism
  • Mice
  • Sodium Fluoride / pharmacology*


  • Cariostatic Agents
  • Cytokines
  • Dental Enamel Proteins
  • Interleukins
  • Sodium Fluoride
  • L-Lactate Dehydrogenase
  • Alkaline Phosphatase
  • Calcium