Objective To observe changes in mRNA expressions of bone morphogenetic protein Ⅱ (BMP-2), receptor activator of nuclear factor kappa-B (RANK), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt1) in dental tissues of the rats with chronic coexposure to arsenic and fluoride.
Methods Clean Wistar rats were divided randomly into 16 groups by factorial design, with 10 rats in each group (half female and half male), and intragastrically exposed to different doses of NaF (0.0, 5.0, 10.0, and 20.0 mg/kg), NaAsO2 (0.0, 2.5, 5.0, and 10.0 mg/kg), or the combination of NaF and NaAsO2 for 6 days per week and continuously 6 months. The levels of teeth fluoride (TF) and teeth arsenic (TAs) were determined by fluoride ion selective electrode method and atomic fluorescence spetrometry. The mRNA expressions of BMP-2, RANK, PI3K, and Akt1 were detected by quantitative real-time PCR.
Results There was no dental fluorosis found in the four groups without fluoride exposure, but in the other 12 groups with fluoride exposure. TF and TAs levels increased with higher independent fluoride or arsenic exposure doses. The mRNA expression levels of BMP-2 and Akt1 in dental tissues of rats increased with higher fluoride exposure doses (P<0.05), but not changed with higher arsenic exposure doses (P>0.05). The mRNA expression levels of RANK and PI3K in dental tissues of rats decreased with higher fluoride exposure doses (P<0.05), but did not change with higher arsenic exposure doses (P>0.05). Fluoride exposure doses and dental fluoride levels were positively associated with the mRNA expression of BMP-2 or Akt1 (r=0.382, 0.302, 0.292, or 0.246, Ps<0.05), but negatively associated with the mRNA expression of RANK or PI3K (r=-0.323, -0.332, -0.193, -0.185, Ps<0.05). Dental fluorosis was negatively associated with the mRNA expression of RANK or PI3K (r=-0.283 or -0.273, Ps<0.05). No association was found between other indicators.
Conclusion Exposure to excessive fluoride can affect teeth enamel development or mineralization and induce dental injury by up-regulating the transcription level of BMP-2 and Akt1 and reducing the transcription level of RANK and PI3K in rat dental tissues. Fluoride plays a key role in dental fluorosis caused by joint exposure to fluoride and arsenic, and arsenic is indirectly involved in developing dental fluorosis.
DownLoad: