Microbiota-Derived Metaboliteoxopaesuppresed Dentin Ecm Formation Via Epigenetics

The microenvironment at dentin-pulp complex could directly interfere dental homeostasis and regeneration post-inefction. This study aims to characterize the microbial and metabolomics profiles of carious dentin, while elucidating the effect of microbiota-derived metabolites on caries progression and the underlying molecular mechanisms. Collected human lesioned dentin samples for metagenomics and metabolomics analysis. Isolated human dental pulps and performed mineralization inducing to obtain human odontoblast-like cells(hODOs). Stimulated hODOs with Porphyromonas gingivalis(P.g) supernatant or P.g-derived metabolite oxoPAE, using histological staining to observe ECM formation, using qPCR and WB to analysis related gene and proteins expression changes. Collected total RNA for transcriptomics to unveil genes and pathways that changed most significantly after stimulation. Collected total histone and perform western blot to unveil histone modification changes. Established WDR5, MLL1 and IκBζ expression plasmids, co-transfection plasmids into HEK293 cells and perform immunoflurescence. This work characterized the microbe and metabolites in lesioned dentin. Further study identified P.g derived metabolite oxoPAE which suppressed the transcription and translation of ECM gene COL1A1 in human odontoblast. oxoPAE stimulation active NFκB pathway, potentially by Palmitoylation, and up-regulated expression of IκBζ, which negatively regulated ECM related gene expression by interference histone H3 try-methylation at K4. Furthermore, in IκBζ-overexpressing cells, WDR5—a component of the methyltransferase complex—was observed to co-localize outside the nucleus with IκBζ, reflecting methyltransferase formation disturbing. P.g derived metabolite oxoPAE via epigenetical modulation contributes to tooth decay development.