Abstract
Fusobacterium nucleatum (F. nucleatum) plays key roles in the initiation and progression of periodontitis. However, the pathogenic effect of F. nucleatum on human oral tissues and cells has not been fully evaluated. In this study, we aimed to analyze the pathogenic effects of F. nucleatum on human gingival fibroblasts (GFs) and clarify the potential mechanisms. RNA-sequencing analysis confirmed that F. nucleatum significantly altered the gene expression of GF as the stimulation time increased. Cell counting and EdU-labeling assays indicated that F. nucleatum inhibited GF proliferation and promoted cell apoptosis in a time- and dose-dependent manner. In addition, cell apoptosis, intracellular reactive oxygen species (ROS) generation, and proinflammatory cytokine production were dramatically elevated after F. nucleatum stimulation. Furthermore, we found that the AKT/MAPK and NF-κB signaling pathways were significantly activated by F. nucleatum infection and that a large number of genes related to cellular proliferation, apoptosis, ROS, and inflammatory cytokine production downstream of AKT/MAPK and NF-κB signaling pathways were significantly altered in F. nucleatum-stimulated GFs. These findings suggest that F. nucleatum inhibits GF proliferation and promotes cell apoptosis, ROS generation, and inflammatory cytokine production partly by activating the AKT/MAPK and NF-κB signaling pathways. Our study opens a new window for understanding the pathogenic effects of periodontal pathogens on the host oral system.
Highlights
Periodontal diseases are prevalent globally, with approximately 60% of the adult population suffering from mild, moderate, or aggressive periodontitis [1, 2]
The correlation analysis of the principal component analysis (PCA) on the whole-genome gene expression levels showed that the normal cells were relatively stable, while the F. nucleatumstimulated gingival fibroblasts (GFs) gradually deviated from normal conditions as the stimulus time increased (Supplementary Figure 1)
These results suggest that the effect of F. nucleatum stimulation on GFs may accumulate over time
Summary
Periodontal diseases are prevalent globally, with approximately 60% of the adult population suffering from mild, moderate, or aggressive periodontitis [1, 2]. As a chronic inflammatory disease, periodontitis is characterized by the destruction of the gingiva, periodontal ligament, cementum, and alveolar bone and is initiated by the invasion of specific oral pathogens that colonize dental plaque biofilms on the tooth surface [3,4,5]. The pathogenesis of periodontitis is complex, and excessive tissue destruction occurs as a result of interactions between pathogenic bacteria and the host immune inflammatory response [3]. F. nucleatum, as a bridging bacterium, transfers critical periodontal pathogens to periodontal infectious sites and recruits and activates local immune cells, which results in tooth-supporting tissue destruction [10, 11]. The effects of F. nucleatum on gingival fibroblast (GF) proliferation and apoptosis have not been reported
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
