Effect of conditional agrin deletion in osteocytes on bone loss induced by osteoporosis, the repair of osteoporotic bone tissue, and the osteogenic potential of mesenchymal stem cells

• Grant number: 25/00150-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2025
• End date: September 30, 2028
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Márcio Mateus Beloti
• Grantee: Márcio Mateus Beloti
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• City of the host institution: Ribeirão Preto
• Associated researchers: Adalberto Luiz Rosa ; Ana Paula Ramos ; Emanuela Prado Ferraz

Abstract

The maintenance of bone tissue shape and function requires the participation of numerous molecules that regulate bone remodeling. Understanding these molecules and their roles in this process is crucial for elucidating the pathogenesis of several diseases that affect bone tissue and facilitating the discovery of potential therapeutic targets. One such molecule is the extracellular matrix protein agrin (AGRN), which participates in skeletal development and is expressed by chondrocytes, osteocytes, osteoblasts, and mesenchymal stem cells (MSCs). Recent findings from our research group have demonstrated that Agrn deletion in osteocytes affects bone tissue development in male mice but not in female mice. Interactions between MSCs and osteocytes are important for maintaining bone tissue homeostasis, and the disruption of osteocyte function contributes to the development of osteoporosis. Based on these findings, the objectives of this study are to investigate the effects of conditional deletion of Agrn in mouse osteocytes with osteoporosis on (1) morphometric, mechanical, and chemical parameters of bone tissue, (2) bone repair of defects created in calvariae, and (3) osteogenic potential and expression of Agrn and its targets in MSCs derived from bone marrow. The results of this study may have significant scientific and therapeutic implications, as Agrn could serve as a target protein for the development of novel therapeutic strategies that promote osteogenesis, with applications in the treatment of bone defects in challenging sites and bone loss induced by metabolic diseases such as osteoporosis. (AU)