Benjamin Shelling
| Benjamin Shelling |
Benjamin Shelling
Min Jiang, Xia Xia-Juan, Kantapon Rattanaprukskul, Emmanuel Albuquerque-Souza
Sinem Esra Sahingur
Periodontics, University of Pennsylvania, School of Dental Medicine
Introduction
Periodontitis is a highly prevalent, chronic inflammatory disease that causes irreversible damage to the periodontium leading to alveolar bone resorption. It is primarily caused by a robust host response to a dysbiotic microbiome where the presence of keystone pathogens such as Fusobacterium nucleatum is critical. This milieu is expected to trigger a pro-senescence response, although the factors dictating such events in the periodontium are still unknown. Senescent cells and their senescent associated secretory phenotype (SASPs) are chief contributors to a chronic inflammatory state termed as ‘inflammaging’, which can drive aged-associated diseases like periodontitis. Our study was designed to determine whether periodontal bacteria, F. nucleatum, triggers cellular senescence in gingival epithelial cells.
Methods
Telomerase Immortalized Gingival Keratinocytes (TIGKs) were exposed to F. nucleatum at a multiplicity of infection of 1:10 for up to 5 days. Non-challenged cells and cells exposed to a non-pathogenic oral bacteria (Streptococcus sanguinis) were used as controls. The levels of pro-senescence (beta-galactosidase, and p16INK4a) and anti-senescence markers (p14ARF, p53, and Lamin-B1) were assessed using western blotting and immunofluorescence.
Results
Gingival keratinocytes challenged with F. nucleatum exhibited increased levels of p16INK4a and beta galactosidase (pro-senescence markers) and reduced levels of p14ARF, p53 and Lamin B1 (anti-senescence markers). The exposure of gingival keratinocytes to non-pathogenic oral bacteria, Streptococcus sanguinis, had no effect on senescence markers.
Conclusion
Exposure to dysbiotic microbiome can trigger senescence like phenotype in periodontal tissues and possibly contribute to periodontal disease pathogenesis.