Exploring the role of AoSMC-derived small extracellular vesicles in vascular-bone crosstalk under normal and pathological conditions

• Grant number: 25/06351-7
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: October 06, 2025
• End date: October 05, 2026
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Willian Fernando Zambuzzi
• Grantee: Matheus Luquirini Penteado dos Santos
• Supervisor: Juan Manuel Falcon Perez
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Centro De Investigacion Cooperativa En Biociencias, Spain
• Associated to the scholarship: 22/14304-0 - From exosome characterization to monoclonal antibodies (mAb) production: looking for biotechnological strategies to bone disorders treatment, BP.DD

Abstract

Bone remodeling is a tightly regulated process that depends on coordinated interactions between vascular and skeletal systems. Recent findings have highlighted the role of extracellular vesicles (EVs) derived from human aortic smooth muscle cells (AoSMCs) as key modulators of osteoblast differentiation and osteocyte transition, suggesting a novel mechanism of intercellular communication linking vascular dysfunction to bone pathologies. This project aims to elucidate how small extracellular vesicles (sEVs) secreted by VSMCs influence osteogenic differentiation under physiological and pathological conditions, such as vascular calcification and hyperglycemia. To achieve this, AoSMCs will be cultured under different stimuli to mimic healthy and disease- associated environments, and their sEVs will be isolated and characterized using advanced proteomic, metabolomic, and imaging techniques. The impact of these vesicles on osteoblast-to-osteocyte differentiation will be evaluated through functional assays and gene expression analysis. Metabolomic profiling will further identify key bioactive molecules involved in this crosstalk. The research internship at CIC bioGUNE, under the supervision of Professor Juan Manuel Falcón, will allow the application of cutting-edge mass spectrometry platforms and bioinformatic tools for EV analysis, contributing to the refinement of experimental approaches and deepening the understanding of vesicle- mediated signaling. Ultimately, the project seeks to establish a molecular foundation for the future development of monoclonal antibodies targeting vesicle-associated biomarkers, advancing biotechnological strategies for the treatment of bone-related complications linked to metabolic and vascular disorders. (AU)