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Effect of VEs released by osteoblasts on osteoclastogenesis and bone loss in vivo

Grant number: 21/12983-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): December 01, 2021
Effective date (End): November 30, 2024
Field of knowledge:Biological Sciences - Biochemistry - Chemistry of Macromolecules
Principal Investigator:Sandra Yasuyo Fukada Alves
Grantee:Keteryne Rodrigues da Silva
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:19/08568-2 - Investigation of the extracellular vesicles (VEs) role in the initiation, propagation, regeneration, and modeling of biological mineralization, AP.TEM

Abstract

Bone remodeling is a metabolic process desired by a precise balance between degradation (resorption) and synthetic bone matrix. This process involves an orchestrated activity of specialized cells such as osteoblasts and osteoclasts, which ensure the maintenance of bone mass. Thus, an imbalance between the activity of osteoclasts and/or osteoblasts can result in dynamic changes in bone tissue, leading to major osteolytic pathologies. Until recently, communication between cells was thought to occur through direct cell-cell contact (adhesion, interactions) or transfer of soluble mediators, which circulate in blood and body fluids. Recent studies have described that cells can also communicate by cell fragments called Extracellular Vesicles (EVs). For example, exosomes, a type of extracellular vesicle, can coordinate bidirectional and balanced signaling from osteoclasts and osteoblasts, modulating the differentiation and activity of these cell types. It has been shown that exosomes from bone marrow stromal cells may be responsible for bone remodeling by directly regulating the proliferation and activity of osteoblasts in vitro and in vivo. Furthermore, several studies show that exosomes can control osteoclastogenesis, since exosomes derived from osteoblasts and osteocytes may contain RANKL and osteoprotegerin (OPG), which are mandatory mediators for the control of osteoclast differentiation. To date, a growing number of studies have reported that EVs may be involved in bone remodeling and that the content of exosomes can range from proteins, lipids, and nucleic acids. Thus, understanding the complexity of biogenesis, exosome trafficking and their roles on the formation and activation of osteoclasts is a potential field of investigation that can bring important contributions towards containing pathological bone destruction and preventing bone loss. In this context, as part of the thematic project, this subproject will aim to investigate the mechanism by which MVs mediate bone remodeling. (AU)

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