The role of OGT of the osteoclast on experimental bone loss

• Grant number: 17/24073-8
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2018
• End date: February 28, 2021
• 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

Abstract

Bone remodelling is an active and dynamic process that relies on the correct balance between bone resorption by osteoclasts and bone deposition by osteoblasts. When the balance is lost such as in hormone changes situation, infectious process or trauma, an increased osteoclast function could lead to several skeletal pathologies. Using pharmacological tools, our research group evidenced the importance of the enzyme, termed O-linked N-acetylglucosamine transferase (OGT) in the osteoclastogenesis and its function in vitro. In this sense, it is necessary to more deeply understand the biological significance of this protein modification in osteoclasts, regulating physiological and pathological bone remodelling. The findings from this study might provide knowledge to support the development of new preventive or therapeutic targets for osteolitic diseases treatment. Here, we will examine the effect of OGT deficiency in osteoclasts (Ctpsk-Cre OGT-flox and LysM-Cre OGT-flox) using two experimental models of bone loss: ovariectomy-induced osteoporosis and periodontitis model. Specifically, we will assess the effect of the-GlcNAcylation on bone turnover evaluating dynamic bone formation parameters CTX and TRAP (resorption) and BGP and P1NP (bone formation), as well as the presence and activation of osteoclasts by osteoclast signature analysis by PCR, Western Blot and zymography. We will also deeply evaluate the bone loss by histological section and 3D mCT analysis. (AU)

Scientific publications

(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)

DUFFLES, LETICIA FERNANDA; MENINO, ALESSANDRA PARREIRA; TAIRA, THAISE MAYUMI; DE OLIVEIRA, SARAH; SALVADOR, SERGIO LUIZ; MESSORA, MICHEL REIS; AURELIO, MARCO; VINOLO, RAMIREZ; FUKADA, SANDRA YASUYO. Probiotic Bifidobacterium animalis subsp. lactis consumption slows down orthodontic tooth movement in mice. ARCHIVES OF ORAL BIOLOGY, v. 134, p. 7-pg., 2022-02-01. (17/24073-8, 19/11662-0)