Effects of extracellular vesicles on fibroblasts exposed to osteonecrosis-inducing medication

• Grant number: 24/20265-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Taisa Nogueira Pansani
• Grantee: Hugo Mitsuhiro Miyagi
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated research grant: 22/06491-5 - Use of extracellular vesicles to prevent the development of osteonecrosis of the jaws: in vitro and in vivo studies, AP.GR

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a condition characterized by the exposure of bone tissue in the oral cavity, leading to tissue necrosis, in patients who have used antiresorptive medications, such as bisphosphonates and monoclonal antibodies, without a history of head and neck radiotherapy. Bisphosphonates inhibit bone resorption by inducing apoptosis in osteoclasts, whereas denosumab (a monoclonal antibody) blocks their differentiation. However, the accumulation of these drugs in tissues results in decreased local vascularization, tissue toxicity, and delayed tissue repair, leading to the development of osteonecrosis. Recently, the use of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) has emerged as a promising therapy for tissue regeneration. These EVs are biocompatible, have low immunogenicity, and promote cellular differentiation and proliferation. Therefore, the aim of this project was to evaluate the effect of MSC-derived EVs on fibroblasts exposed to zoledronic acid (ZA), either alone or in combination with the monoclonal antibody denosumab (D).