THE STING PATHWAY ON OSTEOCLASTOGENESIS AND DEVELOPMENT OF EXPERIMENTAL PERIAPICAL LESION

• Grant number: 24/02382-2
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): June 01, 2024
• Effective date (End): May 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Maria Luiza Menezes da Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

The periapical lesion stands out among odontogenic infections as a pathology with high global prevalence, and it may be associated with the tooth and its supporting structures. Its etiology is mainly related to the exposure of pulp tissues, and its progression can result in bone loss or the presence of abscesses. The formation of the periapical lesion results from the migration of bacteria towards the dental apex and the host's innate immune response. Among various mechanisms of innate immunity, the cGAS-STING pathway stands out, which is associated with the development of various inflammatory pathologies with outcomes similar to apical periodontitis, such as rheumatoid arthritis and osteoarthritis. The cGAS-STING pathway is responsible for acting on various cellular processes, notably triggering the type I interferon (IFN-I) signaling cascade, as IFN-I plays a regulatory role in osteoclastogenesis and osteoblastogenesis processes. This project aims to analyze the role of the cGAS-STING pathway in bone cells in the development of experimental periapical lesions in mice. Initially, the periapical lesion induction model will be performed by exposing dental pulp in mice deficient in STING in osteoblasts and their respective controls. After 7 and 14 days, the hemimandibles will be collected, processed, and subjected to hematoxylin and eosin (HE) staining and Micro CT for histomorphometric analysis of the periapical lesion. The evaluation of the number of osteoclasts will be assessed by TRAP staining. The analysis of inflammatory infiltrate will also be performed using immunohistochemistry, qPCR, and ELISA techniques. In a second phase, we will evaluate the impact of STING deletion in osteoblasts on the formation and function of osteoclasts (in vitro).