OGT role in osteoclasts from expermental-induced osteoathritis

• Grant number: 17/16666-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: January 01, 2018
• End date: February 22, 2019
• Field of knowledge: Biological Sciences - Pharmacology
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Paulo Vinicius Gil Alabarse
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Osteoarthritis does not have effective treatment, it had been needed research about cell signaling responsible for bone remodeling (e.g. osteoblast and osteoclasts) in order to find therapeutic targets. Osteoclast is cells with high energetic metabolism as well as responsible for bone resorption. The O-GlcNacilation it a protein post-translational modification wherein the OGT enzyme adds O-GlcNac, meanwhile, the OGA enzyme removes it. The hexosamine biosynthetic pathway produces O-GlcNac and it is regulated by glucose availability. There are few studies evaluating O-GlcNacilation, in which it has been inferred a control of differentiation and activity of osteoblasts. Besides, it has been observed an accumulation of O-GlcNacilated proteins in chondrocytes from osteoarthritis patients. Albeit there is research with O-GlcNacilation in osteoblast and chondrocytes, there are few and controversial results in osteoclastogenesis focusing O-GlcNacilation. Until now, it has been evidenced an increase in osteoclast differentiation when added high levels of glucose in culture, as well as resorption inhibition under glucose deprivation. Therefore, the following project has as an aim evaluate the OGT role in osteoclasts under the pathological process of experimental osteoarthritis in mice. Preliminary data had shown that O-GlcNacilation has an important role in differentiation and activity of osteoclasts. Thus, we hope to clarify the O-GlcNacilation role in osteoclastogenesis as well as its mechanisms involved. We hope also to ascertain the importance of OGT knockout in bone loss induced by osteoarthritis.