Role of O-GlcNAcytation on the expression of osteoclast and inflammation marker genes in the periapical lesion model

• Grant number: 19/11099-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2019
• End date: June 30, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Eduardo Luiz Papa Villa
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The periapical lesion is an inflammatory/infectious disease with a high prevalence in the world that starts with the microbial invasion in the pulp tissues spreading to the dental apex. It results in the destruction of the periapical tissue, among them periodontal ligament, cementum, and alveolar bone. During the course of the disease, immune responses and many cell types like osteoclasts, actively participate in periapical alveolar bone resorption. To do so, osteoclasts require a high energy expenditure, since glucose deprivation inhibits bone resorption capacity, while elevated glucose levels increase their differentiation. High glucose levels, such as in hyperglycemia, lead to a change in the hexosamines pathway and, consequently, O-GlcNAcylation, which consists in the incorporation of O-linked-Nacetylglucosamine(O-GlcNAc)in serine and threonine of nuclear and cytoplasmic proteins by the action of the OGT enzyme. O-GlcNAcylation can modulate functions of the target proteins, analogously to the phosphorylation process. Evidence from our research group shows that O-GlcNAcylation of proteins is essential for osteoclastogenesis in vitro and this cell type is crucial for the development of periapical lesion, therefore, the aim of the present work is to evaluate the biological role of O-GlcNAcylation in the development of inflammatory response and bone loss in a periapical lesion model. CtskCre OGTflox/flox and CtskCreOGT0/0 animals will be used and the expression of osteoclast markers, as well as the expression of inflammatory cytokines in the jaw samples, will be evaluated, both by realtime PCR.