EFFECT OF THE SENOLYTIC COMBINATION DASATINIB AND QUERCETIN ON INDUCED PERIODONTITIS IN MICE

• Grant number: 22/16810-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: June 30, 2024
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Ana Lia Anbinder
• Grantee: Yuri Cavalcante Santos
• Host Institution: Instituto de Ciência e Tecnologia (ICT). Universidade Estadual Paulista (UNESP). Campus de São José dos Campos. São José dos Campos , SP, Brazil

Abstract

Cell senescence is characterized by the irreversible arrest of the cell cycle with establishment of the senescence-associated secretory phenotype (SASP) and production of cytokines that, if not efficiently eliminated, are a source of chronic inflammation. Senolytics induce senescent cells to apoptosis, and their use has been encouraging in studies of systemic age-related bone loss. Combination therapy with the tyrosine kinase inhibitor Dasatinib and the plant flavonoid Quercetin (D&Q) has been evaluated in several conditions and has attenuated the age-related bone loss in preclinical models. An accumulation of senescent osteocytes in alveolar bone was reported in young mice, and such cells produced inflammatory cytokines in vitro, providing a pro-osteoclastogenic environment that could contribute to periodontitis. However, these findings are associative, and it has not been experimentally evaluated whether (and to what extent) senescence in alveolar osteocytes causes alveolar bone loss (ABL). Our general hypothesis is that osteocytic senescence is one of the causes of alveolar bone loss and that senolytics may offer protection in the context of ABL associated with periodontitis. Mice will be divided into 3 groups, according to the induction of periodontitis by ligature insertion and Porphyromonas gingivalis infection and treatment with D&Q: 1-Control group, without induced periodontitis; 2-Experimental periodontitis group (EP); 3-Group D&Q, with PE and treated with D&Q (5mg/kg and 50mg/kg; respectively). The animals will be euthanized 30 days after the ligature insertion and alveolar bone loss will be evaluated using computed microtomography and histometrical analysis. Data will be evaluated with the appropriate statistical method.