The Molecular Mechanism of Enamel Matrix Proteinases Regulated by FoxO1 in Dental Fluorosis

Objectives: The present study aimed to observe the regulating mechanism of FoxO1 on enamel matrix proteinases MMP20 and KLK4 in dental fluorosis.
Methods: LS8 cells were exposed to sodium fluoride (NaF) at selected concentration (0/1/2 mM) for 24 hours. FoxO1, MMP20, KLK4 mRNAs and protein expression were measured by real-time RT-PCR and western blot. Lentivirus vector containing FoxO1 was used to upregulate FoxO1 in LS8 cells. The effect of FoxO1 up-regulation on KLK4 and MMP20 expression was examined by real time RT-PCR and western blot.
Results: Down-regulation of FoxO1, KLK4 was observed under sodium fluoride treatment in LS8 cells (P < 0.05). However, MMP20 was not markedly changed. After lentivirus transfection, FoxO1 expression was significantly increased (P < 0.05). Overexpression of FoxO1 upregulated the expression of KLK4 (P < 0.05). However, the variation trend of MMP20 was not clear.
Conclusions: Fluoride may reduce FoxO1 expression or activity, which influences the expression of KLK4 and causes dental fluorosis.