The role of O-glycosylation on the modulation of osteoclastogenesis and bone resorption

• Grant number: 15/09034-0
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2015
• End date: November 30, 2017
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Sandra Yasuyo Fukada Alves
• Grantee: Sandra Yasuyo Fukada Alves
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 16/50332-8 - The role of O-GlcNAcylation in the host immune response and bone resorption, AP.R SPRINT

Abstract

An increasing number of evidence indicates that glucose plays a role far beyond the traditional biological role in energy metabolism, since it can also modulate various protein properties. Recent studies have shown that the O-GlcNacylation, a post-translational modification of proteins regulates cytoplasmic and nuclear target proteins functions. It is analogous to phosphorylation and involves the incorporation of O-GlcNac (O-linked N-acetylglucosamine ²-), on serine and threonine residues by OGT. 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, control the intracellular level of UDP-GlcNac and therefore the O-GlcNacylation protein. Since hyperglycemia and hexosamine biosynthetic pathway modifications are observed in diabetes, it is reasonable to suggest that protein O-GlcNacylation may be involved in the complications observed in this pathology. Among these complications, numerous studies show that diabetic patients present a significant bone loss as well as greater prevalence and severity of periodontal disease. To date, few studies have shown the role of O-GlcNacylation regulating bone remodeling. Although, some studies have shown that O-GlcNacylation is able to increase osteoblasts differentiation and activation, and our previous data showing that protein modification induced by O-GlcNacylation positively regulate osteoclasts diferenciation, there is no data in the literature that show the role of O-GlcNacylation on osteoclastogênesis. Therefore, our aim is to evaluate the effect of O-GlcNacylation in osteoclasts differentiation and activation. In addition, the project also aims to evaluate the participation of glucose-sensitive pathways changes (O- GlcNacylation protein) in the pathophysiology of bone loss in diabetes. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

RAMOS-JUNIOR, ERIVAN S.; LEITE, GISELE A.; CARMO-SILVA, CECILIA C.; TAIRA, THAISE M.; NEVES, KARLA B.; COLON, DAVID F.; DA SILVA, LEA A. B.; SALVADOR, SERGIO L.; TOSTES, RITA C.; CUNHA, FERNANDO Q.; et al. Adipokine Chemerin Bridges Metabolic Dyslipidemia and Alveolar Bone Loss in Mice. Journal of Bone and Mineral Research, v. 32, n. 5, p. 974-984, MAY 2017. (15/09034-0, 13/08216-2, 12/50842-5, 14/11958-3)

BORGHI, SERGIO M.; MIZOKAMI, SANDRA S.; PINHO-RIBEIRO, FELIPE A.; FATTORI, VICTOR; CRESPIGIO, JEFFERSON; CLEMENTE-NAPIMOGA, JULIANA T.; NAPIMOGA, MARCELO H.; PITOL, DIMITRIUS L.; ISSA, JOAO P. M.; FUKADA, SANDRA Y.; et al. The flavonoid quercetin inhibits titanium dioxide (TiO2)-induced chronic arthritis in mice. JOURNAL OF NUTRITIONAL BIOCHEMISTRY, v. 53, p. 81-95, MAR 2018. (15/09034-0, 10/15014-9)

CARVALHO, ADRIANA L.; MASSARO, BIANCA; E SILVA, LUCIANA T. P.; SALMON, CARLOS E. G.; FUKADA, SANDRA Y.; NOGUEIRA-BARBOSA, MARCELLO H.; ELIAS, JR., JORGE; FREITAS, MARIA C. F.; COURI, CARLOS E. B.; OLIVEIRA, MARIA C.; et al. Emerging Aspects of the Body Composition, Bone Marrow Adipose Tissue and Skeletal Phenotypes in Type 1 Diabetes Mellitus. JOURNAL OF CLINICAL DENSITOMETRY, v. 22, n. 3, p. 420-428, JUL-SEP 2019. (15/09034-0, 14/14505-0, 14/15864-3, 13/09853-6)

LIMA, VILMA; MELO, IRACEMA MATOS; TAIRA, THAISE MAYUMI; WILCHES BUITRAGO, LISETH YAMILE; RORIZ FONTELES, CRISTIANE SA; ALMEIDA MOREIRA LEAL, LUZIA KALYNE; DE QUEIROZ SOUZA, ANA SHEILA; ALMEIDA, TALYSSON SILVA; DA COSTA FILHO, RAIMUNDO NOGUEIRA; MORAES, MANOEL ODORICO; et al. Uncaria tomentosa reduces osteoclastic bone loss in vivo. Phytomedicine, v. 79, DEC 2020. (15/09034-0, 13/08216-2)

CRUZ, MARCOS A. E.; TOVANI, CAMILA B.; FAVARIN, BRUNO Z.; SOARES, MARIANA P. R.; FUKADA, SANDRA Y.; CIANCAGLINI, PIETRO; RAMOS, ANA P.. Synthesis of Sr-morin complex and its in vitro response: decrease in osteoclast differentiation while sustaining osteoblast mineralization ability. JOURNAL OF MATERIALS CHEMISTRY B, v. 7, n. 5, p. 823-829, FEB 7 2019. (15/09034-0, 17/08892-9, 14/24249-0, 16/21236-0, 15/08774-0)

ARID, JULIANA; XAVIER, THAIS APARECIDA; BEZERRA DA SILVA, RAQUEL ASSED; DE ROSSI, ANDIARA; BEZERRA DA SILVA, LEA ASSED; MUSSOLINO DE QUEIROZ, ALEXANDRA; GALO, RODRIGO; ALVES ANTUNES, LIVIA AZEREDO; BARBOSA SILVA, MARCELO JOSE; ANTUNES, LEONARDO SANTOS; et al. RANKL is associated with persistent primary teeth and delayed permanent tooth emergence. International Journal of Paediatric Dentistry, v. 29, n. 3, p. 294-300, MAY 2019. (15/09034-0, 15/06866-5)

TAIRA, T. M.; LIMA, V; PRADO, D. S.; SILVA, T. A.; ISSA, J. P. M.; DA SILVA, L. A. B.; ZAMBONI, D. S.; CUNHA, F. Q.; FUKADA, S. Y.. NLRP12 Attenuates Inflammatory Bone Loss in Experimental Apical Periodontitis. JOURNAL OF DENTAL RESEARCH, v. 98, n. 4, p. 476-484, APR 2019. (13/08216-2, 15/09034-0)

WILCHES-BUITRAGO, L.; VIACAVA, P. R.; CUNHA, F. Q.; ALVES-FILHO, J. C.; FUKADA, S. Y.. Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-kappa B/NFATc-1. Inflammation Research, v. 68, n. 5, p. 415-421, MAY 2019. (15/09034-0, 13/08216-2)

XAVIER, THAIS APARECIDA; MADALENA, ISABELA RIBEIRO; BEZERRA DA SILVA, RAQUEL ASSED; BEZERRA DA SILVA, LEA ASSED; BARBOSA SILVA, MARCELO JOSE; DE ROSSI, ANDIARA; KUCHLER, ERIKA CALVANO; FUKADA, SANDRA YASUYO. Vitamin D deficiency is a risk factor for delayed tooth eruption associated with persistent primary tooth. ACTA ODONTOLOGICA SCANDINAVICA, v. 79, n. 8, p. 600-605, NOV 17 2021. (15/09034-0, 15/06866-5)