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JNK Signaling Pathway Mediates Fluoride-Induced Upregulation of CK1a during Enamel Formation.Abstract
Fluorosis is a defect in the enamel mineral content caused by excessive fluoride intake during amelogenesis; the interaction of various factors in the development and progression of fluorosis has not been defined. Casein kinase 1a (CK1a) is constitutively active in cells and is involved in diverse cellular processes; however, its expression in fluorosis has not been measured. This study aimed to investigate the effects of fluoride on CK1a expression and to assess the regulation of molecular signaling involving fluoride and CK1a during enamel development. Kunming mice were randomly divided into the control and F groups with induced clinical features of fluorosis. The F group mice, including mothers and newborns, were treated with 50 ppm fluoridated water. Immunohistochemical staining of the sections of the embryonic mandible regions was performed at the bell stage. Protein expression and signaling pathways in a mouse-derived ameloblast-like cell line (LS8) exposed to fluoride or a Jun N-terminal kinase (JNK) inhibitor were compared to those in control cells without exposure. CK1a and proteins of the JNK signaling pathways were assayed by quantitative real-time PCR and Western blotting. Mice of the F group developed dental fluorosis. Scanning electron microscopy showed a significant reduction in the degree of mineralization in the F group mice, which manifested as thin, loosely arranged, and disorganized enamel rods. Additional analysis revealed that the expression of CK1a in the F group was significantly elevated compared with that in the control group; LS8 cells responded to fluoride by upregulation of CK1a expression through the JNK pathway. Our findings identified the potential effects of CK1a on fluorosis using a mouse model and revealed that a high fluoride level increases the expression of CK1a and that JNK can be a key regulatory factor in CK1a expression.
Keywords: Amelogenesis; Casein kinase 1a; Fluorosis; Tooth development; c-Jun N-terminal kinase signaling pathway.
*Original abstract online at https://pubmed.ncbi.nlm.nih.gov/33827100/