Ers Induced Autophagy Protects Via Grp78/Ire1 In Dental Fluorosis

To study the expression changes of GRP78 and p-IRE1 when endoplasmic reticulum stress occurs in ALC, and to explore the regulation of autophagy and apoptosis mechanisms on ameloblast cells after the occurrence of stress. Mature ameloblast-like cells (ALCs) were treated with 0, 1.0 or 2.0 mmol/L sodium fluoride, and C57BL/6 mice (6 weeks old) were treated with 0, 50, 100, or 150 mg/L sodium fluoride to evaluate NaF-induced endoplasmic reticulum stress, apoptosis and autophagy in ameloblast cells. Animal experiments showed that when the exposure 100 mg/Lsodium fluoride, brownish stripes appeared at the incisal end of the mouse teeth; the immunofluorescence and Western blotting results showed that the expressions of GRP78, p-IRE1, LC3 and Beclin1 were dose-dependently upregulated, and reaching a peak at 100 mg/L. Western blotting results of ALCs treated with 2.0 mmol/L sodium fluoride showed that the expressions of LC3, cleaved caspase-3 and cleaved caspase-12 were upregulated, the expression of p62 was downregulated. 4-PBA can alleviate the autophagy and apoptosis caused by stress. Our results demonstrated that fluoride exposure induced ER stress-mediated apoptosis and autophagy in ameloblast. In addition, autophagy plays a protective role in dental fluorosis. This study suggests that GRP78/IRE1 may be potential targets for the prevention and treatment of dental fluorosis.