The role of the osteocyte proteins in the pathophysiology of the chronic kidney disease and mineral bone disorders

• Grant number: 20/13332-5
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2021
• End date: January 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Vanda Jorgetti
• Grantee: Vanda Jorgetti
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Luciene Machado dos Reis ; Rosa Maria Affonso Moysés

Abstract

Osteocytes represent about 95% of bone cells. They are located in mineralized bone tissue and connect with each other, with osteoblasts, osteoclasts, blood vessels and bone marrow cells. These cells express several proteins that act in the regulation of bone remodeling; in phosphorus metabolism; and some of these proteins may participate in the formation of dendritic processes during the differentiation from osteoblasts into osteocytes. Mineral metabolism disorders in chronic kidney disease destabilize the balanced functioning of bone tissue. This imbalance results in impairments in remodeling, mineralization and bone volume and has been studied in patients with chronic kidney disease without particularizing the etiology of kidney disease, such as Diabetes Mellitus, the high prevalence of Mixed Bone Disease, and iron overload observed in some of these patients. Our goal is to study the expression of proteins produced by osteocytes that act on bone remodeling (sclerostin, RANKL, osteoprotegerin, DKK1); regulate phosphorus metabolism and bone mineralization (DMP-1, MEPE, PHEX and FGF23); and that are related to the formation (dendritic processes) of these cells and their cytoskeletal function (E11 / podoplanin and CD44) in the bone tissue of patients whose etiology of kidney disease is DM, patients with mixed bone disease and those with iron overload. Once differences were detected, if they could explain the pathophysiological mechanisms involved, thus allowing better treatment for these patients. (AU)