Proteomic Signatures of Dental Enamel Hypomineralization: Divergent Molecular Pathways in Coal-Burning vs. Drinking-Water Fluorosis.

Exposure to excessive fluoride can lead to dental enamel hypomineralization, which is characterized by the retention of enamel matrix proteins (EMPs). However, the types and functions of EMPs from different fluoride exposure routes remain elusive. In this study, moderate-to-severe coal-burning dental fluorosis enamel (CDF), drinking-water dental fluorosis enamel (WDF) and healthy permanent dental enamel (H) were obtained from the teeth of residents (local until age 12). The EMPs were extracted, digested, and analyzed via nanoLC-HRMS/MS, followed by database searching and bioinformatics; 404, 100, and 293 unique proteins were identified in CDF, WDF and H, respectively. Compared with WDF and H, CDF exhibited the expression of more specific proteins and upregulated proteins. Compared with H, both WDF and CDF upregulated S100 calcium-binding protein and ECM-receptor interactions pathways, but CDF upregulated the expression of more proteins related to calcium ions and serine proteinase inhibitors. Interestingly, compared with H, CDF uniquely activated the Ras signaling pathway and the glycolysis and gluconeogenesis pathways, while TGF-β/Wnt pathways (β-catenin-linked) distinguished CDF from WDF. The proteomic comparisons reveal the effects of fluoride exposure on enamel proteomic signatures, and aid in understanding the essential characteristics and molecular-level differences underlying enamel damage caused by different exposure routes.