Effects of Ionizing Radiation on Vesicle-Guided Bone Mineralization: Therapeutic Perspectives

• Grant number: 24/04140-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2024
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Pietro Ciancaglini
• Grantee: Iara Souza Lima
• Host Institution: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (FFCLRP). 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

Due to long periods in space and exposure to considerable doses of radiation, astronauts sent on long-term missions tend to have bone problems when they return to the planet. Furthermore, osteoradionecrosis is a common sequelae of radiotherapy for head and neck cancer. One of the main problems described is the decrease in bone density, which can result in fragility and fractures. Despite being a real practical problem, studies on the effect of ionizing radiation on metabolism and bone structure are scarce and its mechanisms are poorly described in the literature. This project aims to investigate the impacts of ionizing radiation, covering gamma ray and X-ray sources, on bone mineralization mediated by extracellular vesicles (EVs), both matrix vesicles (MVs) and extracellular vesicles present in the environment (MEVs). . Focusing on analyzing the mineralizing potential of irradiated osteoblastic cells, the study aims to isolate and characterize the EVs involved in this unique process. Through a comprehensive and innovative approach, the project seeks to expand the understanding of the mechanisms underlying this little-explored phenomenon, opening new perspectives for the development of therapeutic strategies aimed at bone health in challenging situations of exposure to ionizing radiation. The project aims to fill this knowledge gap, providing a significant contribution to understanding the impacts of radiation on EVs. Furthermore, we sought to investigate the therapeutic potential of vesicles from irradiated healthy osteoblasts (MC3T3-E1) in the treatment of cells exposed to radiation, using human osteogenic sarcoma cells (OSAS-2) as a cancer model. The goal is to determine whether vesicles irradiated from healthy MC3T3-E1 cells will carry essential molecules with the potential to trigger a variety of responses in cancer cells, from protection against the effects of radiation to inducing cell death or changes in cell behavior. Investigating these effects may provide valuable information for the development of more effective and personalized therapeutic strategies in the treatment of OSAS-2 human osteogenic sarcoma cancer. This research has the potential to advance basic understanding and therapeutic strategies aimed at preserving bone health in the context of ionizing radiation exposure. The study combines the experience of the post-doctoral candidate researcher in radiation physics, with the expertise of the guiding group in bone mineralization and matrix vesicles (Thematic Project 2019/08568-2).