Role of angiotensin ii and angiotensin 1-7 on the metabolism of human bone cells

• Grant number: 18/23934-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: February 01, 2019
• End date: January 31, 2020
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Carlos Ferreira dos Santos
• Grantee: Thais Francini Garbieri
• Supervisor: Maria Helena Raposo Fernandes
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Institution abroad: Universidade do Porto (UP), Portugal
• Associated to the scholarship: 17/19227-6 - Investigation of the modulation of the inflammatory response in human oral and immunological cells by Ang II and Ang 1-7, BP.DR

Abstract

In the field of dentistry, there is an intense search for better understanding of the relationship between the inflammatory response and bone metabolism, in chronic and infectious diseases scenario. The Renin-Angiotensin System (RAS), in addition to regulating various physiological functions such as those related to blood pressure and cardiovascular system, has been reported as an important modulator of inflammatory and immunological processes, and its components can exert pro or anti- inflammatory diseases in a systemic or local way. Mainly Angiotensin II (Ang II), has been related to important alterations in bone metabolism and in the pathogenesis of inflammatory bone disorders, such as osteoporosis. Considering the hypothesis of this work, that human bone metabolism can be altered differently by the ECA / Ang II / AT1, ECA / Ang II / AT2 and ECA2 / Ang 1-7 / MAS axes of the RAS, and that a (osteoblasts and osteoclasts) stimulated with Angiotensin II (Ang II) and angiotensin I-7 (Ang 1-7). The aim of this project is to investigate in vitro, possible alterations in the metabolism of human bone cells (osteoblasts and osteoclasts) after interaction with their respective receptors, followed or not by their pharmacological blockade with Losartan, PD123177 and A779. For this, cultures and isolated cultures of osteoblasts and human osteoclasts will be performed. Viability and cellular cytotoxicity will be assessed by the alamarBlue and Live / Dead assay. After stimulation, gene expression and protein production of osteoblastic and osteoclastic mediators, as well as matrix metalloproteinases (MMPs) and protein quantification of AT1, AT2 and MAS receptors, will be performed by Quantitative Polymerase Chain Reaction (qPCR) preceded by Transcription Reverse (RT), ELISA (Enzyme-Linked Immunosorbent Assay) and flow cytometry. Osteoclastic activity will also be analyzed by activity and labeling of tartrate resistant acid phosphatase (TRAP) as well as osteoblastic activity by colorimetric assays for alkaline phosphatase (ALP). (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)

GARBIERI, THAIS FRANCINI; MARTIN, VICTOR; SANTOS, CARLOS FERREIRA; GOMES, PEDRO DE SOUSA; FERNANDES, MARIA HELENA. The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue. PHARMACEUTICALS, v. 14, n. 5, MAY 2021. (15/03965-2, 17/19227-6, 18/23934-2)

PINHO, LAURA COSTA; GARBIERI, THAIS FRANCINI; GRENHO, LILIANA; ALVES, MARTA M.; SOUSA GOMES, PEDRO; SANTOS, CARLOS FERREIRA; FERNANDES, MARIA HELENA; SANTOS, CATARINA; COLACO, BRUNO. Rosehip Extract-Functionalized Magnesium Hydroxide Nanoparticles and Its Effect on Osteoblastic and Osteoclastic Cells. MATERIALS, v. 14, n. 15, AUG 2021. (15/03965-2, 17/19227-6, 18/23934-2)