Uncoupling protein-2 is an antioxidant that is up-regulated in the enamel organ of fluoride-treated rats

Connect Tissue Res. 2014 Aug;55 Suppl 1(0):25-8. doi: 10.3109/03008207.2014.923854.


Dental fluorosis is characterized by subsurface hypomineralization and retention of enamel matrix proteins. Fluoride (F(-)) exposure generates reactive oxygen species (ROS) that can cause endoplasmic reticulum (ER)-stress. We therefore screened oxidative stress arrays to identify genes regulated by F(-) exposure. Vitamin E is an antioxidant so we asked if a diet high in vitamin E would attenuate dental fluorosis. Maturation stage incisor enamel organs (EO) were harvested from F(-)-treated rats and mice were assessed to determine if vitamin E ameliorates dental fluorosis. Uncoupling protein-2 (Ucp2) was significantly up-regulated by F(-) (∼1.5 & 2.0 fold for the 50 or 100 ppm F(-) treatment groups, respectively). Immunohistochemical results on maturation stage rat incisors demonstrated that UCP2 protein levels increased with F(-) treatment. UCP2 down-regulates mitochondrial production of ROS, which decreases ATP production. Thus, in addition to reduced protein translation caused by ER-stress, a reduction in ATP production by UCP2 may contribute to the inability of ameloblasts to remove protein from the hardening enamel. Fluoride-treated mouse enamel had significantly higher quantitative fluorescence (QF) than the untreated controls. No significant QF difference was observed between control and vitamin E-enriched diets within a given F(-) treatment group. Therefore, a diet rich in vitamin E did not attenuate dental fluorosis. We have identified a novel oxidative stress response gene that is up-regulated in vivo by F(-) and activation of this gene may adversely affect ameloblast function.

Keywords: Enamel; UCP2; fluoride; fluorosis; oxidative stress; vitamin E.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Dental Enamel Proteins / metabolism
  • Enamel Organ / drug effects*
  • Fluorides / pharmacology*
  • Fluorosis, Dental / metabolism*
  • Ion Channels / metabolism*
  • Mice, Inbred C57BL
  • Mitochondrial Proteins / metabolism*
  • Phosphates / pharmacology*
  • Rats, Sprague-Dawley
  • Transcriptional Activation
  • Uncoupling Protein 2
  • Up-Regulation


  • Dental Enamel Proteins
  • Ion Channels
  • Mitochondrial Proteins
  • Phosphates
  • Ucp2 protein, mouse
  • Ucp2 protein, rat
  • Uncoupling Protein 2
  • enamel matrix proteins
  • fluorophosphate
  • Fluorides