Amelogenesis imperfecta is a
congenital disorder within a heterogeneous group of conditions characterized by
enamel hypoplasia. Patients suffer from early
tooth loss, social embarrassment, eating difficulties, and
pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of
amelogenesis imperfecta is complicated by genetic interactions. To identify mouse
amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four distinct groups. To explore how these genes are regulated and affect the phenotype, we predicted
microRNA (
miRNA)-gene interaction pairs using our bioinformatics pipeline. Our
miRNA regulatory network analysis pinpointed that miR-16-5p, miR-27b-3p, and miR-23a/b-3p were hub
miRNAs. The function of these hub
miRNAs was evaluated through ameloblast differentiation assays with/without the candidate
miRNA mimics using cultured mouse ameloblast cells. Our results revealed that overexpression of miR-16-5p and miR-27b-3p, but not miR-23a/b-3p, significantly inhibited ameloblast differentiation through regulation of mAIGenes. Thus, our study shows that miR-16-5p and miR-27b-3p are candidate pathogenic
miRNAs for
amelogenesis imperfecta.