Hsa-miRNA-143-3p Regulates Differentiation of Human Stem Cells From The Apical Papilla Through Targeting Nuclear Factor I-C

Abstract

Background : Dental root development is independent and time-space-specific. Nuclear factor I-C (NFIC) plays a key role in human root development through regulating the differentiation of stem cells from the apical papillary (SCAPs). The function of microRNAs during the differentiation of SCAP and post-transcriptional regulation of NFIC remain unclear. Methods : We examined the microRNA expression profiles in human immature permanent teeth and SCAPs differentiation. hSCAPs were treated with miR-143-3p over/low-expression viruses, and the odonto/osteogenic differentiation of these stem cells and the involvement of NFIC pathway were investigated. Next, luciferase reporter and its mutant plasmids were used to confirm direct target gene of miR-143-3p. Mineralization induction assays ex vivo and in vitro were used to investigate the functional significance of miR-143-3p. Results : MiR-143-3p was screened by microarray expression profiling and bioinformatics technology, which decreased during hSCAPs differentiation. Overexpression of miR-143-3p inhibited the odontogenic differentiation of hSCAPs and downregulated the related genes, whereas the functional inhibition of miR-143-3p yielded the opposite effect. The luciferase reporter gene detection and bioinformatics approach identified NFIC as a potential target of miR-143-3p. Furthermore, NFIC Overexpression reversed the inhibitory effect of miR-143-3p on the odontogenic differentiation of hSCAP. Conclusions : MiR-143-3p maintains the stemness of hSCAPs and negatively modulates their differentiation and mineralization by directly targeting transcription factor NFIC, which serves as an contribution towards a better understanding of the developmental mechanisms of root formation.