The role of O-glycosylation on osteoclastogenesis

• Grant number: 15/09327-8
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2015
• End date: December 31, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Cecília Costa Do Carmo e Silva
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Recent studies have shown that the O-GlcNacylation, a post-translational modification of proteins, analogous to phosphorylation, involves the incorporation of O-GlcNac (O-linked N-acetylglucosamine ²-), on serine and threonine residues. It is controled by OGT and it modifies and regulates cytoplasmic and nuclear target proteins functions. The UDP-GlcNac, the substrate used by OGT for O-GlcNAcylation is produced through the hexosamine biosynthetic pathway which consume a small portion of the glucose entering the cell. The availability of glucose reflects the flux of glucose through this pathway, regulating the intracellular level of UDP-GlcNac and therefore the O-GlcNacylation protein. The reversible and dynamic protein modifications, induced by O-GlcNacylation occur in many cellular dysfunctions observed in several pathologies. To date, few studies have shown the role of O-GlcNacylation regulating bone remodeling cell function. Although, some studies have shown that O-GlcNacylation is able to increase osteoblasts differentiation and activation there is no data in the literature that show the role of O-GlcNacylation on osteoclastogênesis. Therefore, the purpose of this study is to evaluate the effect of O-GlcNacylation in osteoclasts differentiation and activation. For this, O-GlcNacylation will be amplified or inhibited in osteoclasts culture. For osteoclasts differentiation analysis TRAP positive cells were counted and osteoclasts markers expression such as TRAP, NFATc1, vATPase, DC-STAMP, MMP-9, cathepsin k will be evaluated by qPCR. Bone resorption activity will be evaluated by pit resorption formation in osteoassay plate.