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Role of O-GlcNacylation in the bone loss in periapical lesion model

Grant number: 17/23264-4
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2018
Effective date (End): January 31, 2022
Field of knowledge:Health Sciences - Dentistry
Principal researcher:Sandra Yasuyo Fukada Alves
Grantee:Thaise Mayumi Taira
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/15582-1 - The role of O-GlcNAcylation in the osteoclasts fusion and function, BE.EP.DR

Abstract

Periapical lesion is an inflammatory/infectious disease that initiates with the microbial invasion in the pulp tissues and diffuses until the dental apex, resulting in apical tissues destruction. There are many types of cells that participates in this immunoinflammatory process which one are the osteoclasts that actively participate in bone resorption process. To perform such function, osteoclasts require high-energy expenditure, since glucose deprivation inhibits the ability to reabsorb, while elevated glucose levels increase their differentiation. Hyperglycemia alters the hexamine pathway and, consequently, O-GlcNacilation, which consists of the incorporation of O-linked-²-N-acetylglucosamine (O-GlcNac) into serine and threonine residues of nuclear and cytoplasmic proteins by the action of enzyme OGT. O-GlcNacylation regulates functions of the target proteins, analogously to the phosphorylation process. Based on evidence from our research group, O-GlcNacation of proteins is critical for RANKL-induced osteoclastogenesis in vitro and this cell type is crucial for the development of periapical lesion, therefore, the objective of the present work will be to evaluate the role of O-GlcNacylation in the development of inflammatory response and bone loss in a periapical lesion model. For this, Ctsk Cre OGT flox/flox and control animals (Ctsk Cre OGT0/0) will be used and lesion extension by histology and microCT will be evaluated; expression of osteoclasta markers by real-time PCR; the activity of metalloproteinases by Zymography. Furthermore, the periapical lesion characteristics will be evaluated, for example the inflammatory cytokines by ELISA; the neutrophil infiltrate by myeloperoxidase assay. (AU)

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