Background: Upon migrating to the injured sites, bone marrow mesenchymal stem cells (BMSCs) play critical roles in the repair of bone lesion caused by chronic apical periodontitis. Emerging evidences have shown that Enterococcus faecalis is always associated with apical periodontitis, especially refractory apical periodontitis. But the mechanism underlying how Enterococcus faecalis affects the migration of BMSCs remains unclear.
Methods: The effects of Enterococcus faecalis supernatants on the migration of BMSCs were determined by transwell migration assays. miRNA sequencing was performed to detect the significantly differentially expressed miRNAs of BMSCs. Proteomics analysis was used to detect the protein expression alterations of BMSCs. Luciferase report assays were deployed to verify the targets of miRNA. Western blot analysis was performed to examine the expressions of matrix metalloproteinases-3, matrix metalloproteinases-9, Forkhead Box Protein J1 (FOXJ1), and nuclear factor kappa B (NFκB). The activations of NFκB were detected by luciferase assays with NFκBluc reporter.
Results: We found that Enterococcus faecalis supernatants could promote the migration of BMSCs. The upregulation of miR-200a-3p in this process contributed to BMSC migration through downregulating its target Forkhead Box Protein J1. Moreover, FOXJ1/ NFκB axis was found to regulate matrix metalloproteinases (MMPs) in this process.
Conclusions: These results above suggest that miR-200a contributes to the migration of BMSCs induced by the secretions of E. faecalis via FOXJ1/NFκB/MMPs axis.
Keywords: Bone marrow mesenchymal stem cells; Cell migration; Enterococcus faecalis; Host-pathogen interactions; Nuclear factor kappa B; miRNA.