Effect of agrin overexpression in adipose tissue-derived mesenchymal stem cells on osteoblastic and adipocytic differentiation and on bone regeneration

• Grant number: 21/04824-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2022
• Status: Discontinued
• Field of knowledge: Health Sciences - Dentistry - Oral and Maxillofacial Surgery
• Principal Investigator: Márcio Mateus Beloti
• Grantee: Letícia Faustino Adolpho
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 17/12622-7 - Cell therapy: potential of mesenchymal stem cells, VEGF-A and BMP-9 to regenerate bone tissue, AP.TEM
• Associated scholarship(s): 24/00415-0 - Role of agrin receptors in adipose tissue-derived mesenchymal stem cell differentiation in cells of mesenchymal tissues, BE.EP.DR

Abstract

Cell therapy using mesenchymal stem cells (MSCs) is a promising strategy to treat large bone defects and the study of molecules that act on these cells to favor bone regeneration is essential in this context. Our research group have demonstrated that the extracellular matrix protein agrin participates in osteoblastic differentiation, probably by regulating BMP and Wnt signaling pathways, indicating that other pathways could be involved in this process. However, up to now, there is no information in the literature about the effects of agrin on bone formation induced by MSCs derived from adipose tissue, which have the potential to differentiate into osteoblasts and adipocytes. Then, we hypothesized that: 1) agrin overexpression increases the osteogenic potential and reduces the adipogenic potential of MSCs derived from adipose tissue by modulating the signaling pathways of BMPs, Wnt, Notch and Hippo-Yap/Taz and 2) MSCs derived from adipose tissue overexpressing agrin favor bone regeneration. To test these hypotheses, it will be evaluated: 1) the agrin expression during osteoblastic and adipocytic differentiation of MSCs, 2) the effect of agrin overexpression on osteoblastic and adipocytic differentiation of MSCs, 3) the participation of BMP, Wnt, Notch and Hippo-Yap/Taz signaling pathways on the effect of agrin on osteoblastic and adipocytic differentiation of MSCs and 4) the effect of MSCs overexpressing agrin on bone regeneration of mouse calvaria defects. The data generate by this study may contribute to the development of novel therapeutic approaches for bone regeneration.