Use of extracellular vesicles to prevent the development of osteonecrosis of the jaws: in vitro and in vivo studies

• Grant number: 22/06491-5
• Support Opportunities: Generation Project Research Grant
• Start date: November 01, 2023
• End date: October 31, 2028
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Taisa Nogueira Pansani
• Grantee: Taisa Nogueira Pansani
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated researchers: Carlos Alberto de Souza Costa ; Fernanda Gonçalves Basso ; Wojciech Chrzanowski
• Associated scholarship(s): 24/20265-3 - Effects of extracellular vesicles on fibroblasts exposed to osteonecrosis-inducing medication, BP.IC; 24/10548-8 - Effect of extracellular vesicles on osteoblasts exposed to osteonecrosis-related medications, BP.MS; 24/00745-0 - Use of extracellular vesicles to prevent the development of drug-induced osteonecrosis of the jaw: in vitro and in vivo studies, BP.DR; 23/17226-3 - Use of extracellular vesicles to prevent the development of osteonecrosis of the jaws: in vitro and in vivo studies, BP.GR

Abstract

Medication-induced osteonecrosis of the jaw (MRONJ) is a condition in which the patient has exposed bone for more than 8 weeks where they use of drugs as bisphosphonates and denosumab, without previous history of head and neck radiotherapy. These drugs act mainly by inhibiting bone resorption by inducing apoptosis in osteoclasts and inhibiting osteoclast differentiation, however, other effects have been observed, as the reduction of local vascularization. Preventive therapy is essential to reduce the incidence of MRONJ, with dental treatment being indicated before the administration of these drugs and more recently, researchers have suggested therapies that use mesenchymal stem cells (MSC) since these cells play important roles in inducing wound healing. Extracellular vesicles (EVs) are nanoparticles released by cells that contain biomolecules capable of regulating and stimulating different signaling pathways in recipient cells. MSC-derived EVs have numerous advantages such as low immunogenicity, high resistance to hostile environments and bioactivity, playing a crucial role in cell proliferation, angiogenesis and tissue regeneration process. Therefore, the objective of this project will be to evaluate the effect of EVs from MSCs on osteoblasts and oral mucosa cells exposed to zoledronic acid (AZ) associated or not with the monoclonal antibody - denosumab (D), as well as to evaluate the therapeutic effect of EVs in an in vivo model. (AU)