Impact of Sirtuin-1 activation on periodontal microenvironment cells: Implications in the pathogenesis of periodontitis associated or not with diabetes Mellitus.

• Grant number: 25/01198-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2025
• End date: March 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Morgana Rodrigues Guimarães Stabili
• Grantee: Bianca Diaz Paulino de Abreu
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Periodontitis is a chronic, multifactorial inflammatory disease associated with dysbiotic biofilm, characterized by the progressive loss of the tooth attachment apparatus and with high prevalence, mediated mainly by the host's innate immune response to an oral microbial challenge. Diabetes mellitus (DM), in turn, is a metabolic disease characterized by chronic hyperglycemia, resulting from deficient insulin production, resistance to the effects of insulin, or a combination of both. The disease, which can affect quality of life and public health, is associated with a high risk of complications, including macrovascular disease, neuropathy, nephropathy, and delayed wound healing. There is a suggested bidirectional relationship between periodontitis and diabetes, so that periodontal disease (PD) may also contribute to the development of diabetes and vice versa. Sirtuins are a class of enzymes that regulate critical cellular processes such as genome integrity and metabolism, gene silencing, and apoptosis, which have been extensively studied in the regulation of age-related diseases. These proteins are also essential modulators of oxidative stress and inflammation, since they can regulate the expression and activation of transcriptional factors, as well as antioxidant enzymes. Increased expression and activation of sirtuins has been associated with suppression of inflammation in several preclinical and clinical studies of inflammatory diseases. Sirtuin 1 (SIRT1) is the most studied deacetylase of the sirtuin family and is involved in biological processes such as cell differentiation, apoptosis, lipid and sugar metabolism, oxidative stress and inflammation. Inhibition of inflammation of gingival tissues and bone resorption in an experimental model of periodontitis was observed in groups treated with resveratrol, a nonspecific sirtuin activator, through the reduction of oxidative stress. The beneficial effects of SIRT1 activation have also been observed in increasing insulin sensitivity and reducing plasma glucose levels in preclinical studies, demonstrating its promising role in modulating type 2 diabetes. On the other hand, a multifaceted role of SIRT1 has been observed in models of tumorigenesis and infectious processes, indicating that SIRT1 overactivation can lead to immunosuppression and exacerbate the chronicity of inflammatory processes. These results suggest that the beneficial or detrimental effects of pathway activation depend on the microenvironmental conditions and activation dynamics. Considering the protagonism of sirtuins in the regulation of inflammation and oxidative stress, this study aims to investigate the molecular effects of SIRT1 activation in periodontal cells, responsible for bone metabolism and tissue repair, subjected to inflammatory and hyperglycemic conditions.