EFFECTS OF SODIUM FLUORIDE ON THE UNFOLDED PROTEIN RESPONSE SIGNALING PATHWAY IN RAT AMELOBLASTS.

OBJECTIVE : We examined the effects of different concentrations of sodium fluoride on the morphological characteristics and the unfolded protein response signaling pathway (UPR) in rat ameloblasts. METHODS : Eighty Wistar rats were randomly divided into one control and three experimental groups. Rats in each group were fed with water containing fluoride ion (F) concentrations of <0.3 mg F/L (control), 50 mg F/L (low-dose group), 100 mg F/L (middle-dose group), and 150 mg F/L (high-dose group). After 12 weeks of treatment, the rats were killed and each mandible was dissected out for sectioning to observe the characteristic morphology of ameloblasts during tooth development by HE staining. Simultaneously, we analyzed the expression of immunoglobulin binding protein (BiP), X-box binding protein (XBP1), inositol-requiring enzyme 1 (XBIre1 α ), and activating transcription factor 6 (ATF6) in ameloblasts by in situ hybridization. RESULTS : The results indicated that fluoride affects the morphology and differentiation of ameloblasts during tooth development. The mRNA expression of BiP, XBP1, Ire1 α , and ATF6 increased significantly with increasing fluoride concentrations in drinking water (p<0.05 or p<0.01). In addition, the expression of these proteins increased gradually, but significantly, with tooth development in a dose-dependent manner in the experimental groups, particularly at the transition and maturity periods (p<0.05 or p<0.01). CONCLUSION : Our study suggests that fluoride undermined the morphology and differentiation of ameloblasts during tooth development and initiated an endoplasmic reticulum (ER) stress response. UPR responses play a role in the development of dental fluorosis and might lead to dental fluorosis. [ABSTRACT FROM AUTHOR]