Proteomics of enamel in Molar Incisor Hypomineralization

Abstract

Molar incisor hypomineralization (MIH) is a compositional enamel defect with disturbed mineral maturation and an altered mineral–organic balance. This thesis aimed to deepen proteomic understanding of enamel by characterizing organic components in MIH and testing whether alterations extend beyond the visible borders of demarcated opacities. Extracted permanent teeth from children aged 8–14 years were studied: first permanent molars with MIH and premolars and molars with healthy enamel as controls. Undecalcified enamel was micro-sampled for quantitative LC–MS proteomics. Confocal micro-Raman spectroscopy mapped mineral chemistry and structure across opacity borders. Paper I established a reproducible LC–MS workflow for sound enamel. Paper II used quantitative proteomics to distinguish MIH from normal enamel and to assess variation with clinical severity. Paper III applied micro-Raman mapping to determine whether mineral changes extend beyond the visible margins, in addition, Paper IV used LC–MS to analyze whether proteomic alterations show a similar spatial pattern. Enamel proteomics in undecalcified human teeth was feasible and biologically informative. MIH enamel displayed a distinct proteomic profile and heterogeneity related to different severity grades. Micro-Raman analyses revealed compositional and structural gradients that could extend into enamel adjacent to the visible opacity, consistent with a mineral transition zone. In compare, proteomic changes were most pronounced within the opacity, whereas enamel sampled beyond the visible border resembled healthy enamel. These results indicate different spatial patterns for inorganic and organic alterations in MIH. The thesis supports combining spatially resolved mineral analyses with proteomics to capture heterogeneity of MIH opacities.