Kantapon Rattanaprukskul
| Kantapon Rattanaprukskul |
Kantapon Rattanaprukskul, Min Jiang, Xia-Juan Xia, Benjamin Shelling, Emmanuel Albuquerque-Souza, Sinem, Esra Sahingur
Periodontics, University of Pennsylvania, School of Dental Medicine
Introduction
Persistent chronic inflammation, microbial exposure, and oxidative stress as seen in periodontitis can trigger aging-like phenomenon. Cellular senescence is one of the hallmarks of aging tissues and characterized by the arrest of cellular growth and multi-level metabolic alterations. Increase in senescent cells and up-regulation of senescence-associated secretory phenotype are associated with aged-related diseases. Targeting senescence by a new class of agents termed senomorphic agents show promise in improving clinical outcomes. This can apply to periodontal health as well. We hypothesized that periodontitis triggers senescence phenotype in the oral mucosa and that targeting senescence as a therapeutic option can improve disease outcomes. Our objective was to assess the expression of senescence markers (SA-β-gal and p16) in the periodontal tissues using clinical biopsies and determine the effect of senomorphic drug combination (dasatinib and quercetin) on bacteria-induced senescence in human gingival keratinocytes (TIGKs).
Methods
Healthy and periodontitis gingival tissue biopsies were obtained from the younger (< 55 years old) and older (≥ 55 years old) patients. The relative mRNA level of p16 and SA-β-galactosidase protein were determined using real time PCR and immunohistochemistry, respectively. Senescence was induced in TIGKs through exposure to periodontal bacteria, Fusobacterium nucleatum, with or without treatment with dasatinib & quercetin. The effect of dasatinib & quercetin treatment on senescence markers (p16 and β-galactosidase) were evaluated using western blotting and immunohistochemistry.
Results
Clinically, we noted increased p16 expression and SA -β-galactosidase activity in periodontitis lesions compared to healthy samples. In vitro, the treatment of gingival keratinocytes with dasatinib and quercetin resulted in reduced expression of senescence markers (p16 expression and SA -β-galactosidase) compared to control cells which were treated with vehicle.
Conclusion
Prolong exposure to dysbiotic periodontal environment can cause senescence like changes and contribute to periodontal disease pathogenesis. Targeting senescence can be a novel and alternative option to better manage the disease and improve clinical outcomes.