MicroRNAs role in bone impairment induced by periodontal disease and the local renin-angiotensin system in spontaneous hypertensive rats

• Grant number: 18/23676-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): March 01, 2020
• Effective date (End): June 30, 2023
• Field of knowledge: Health Sciences - Dentistry
• Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Sandra Helena Penha de Oliveira
• Grantee: Victor Gustavo Balera Brito
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated research grant: 15/03965-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach, AP.TEM
• Associated scholarship(s): 21/09597-6 - Characterization of microRNAs predicted to have functional effects on bone formation and bone loss, BE.EP.DR

Abstract

Periodontal disease (PD) is an inflammatory disorder of the teeth surrounding and supporting tissues. Although the microbial etiological factor is determinant, PD progression depends on a dynamic pathogen-host interaction and may be aggravated by pre-existing systemic diseases such as hypertension, with a high probability of coexistence with PD, as they share several risk factors. In addition, studies discuss a possible causality between hypertension and PD, showing a two-way relationship when associated. In Spontaneously Hypertensive Rats (SHR), an important model of essential hypertension, PD show an exacerbated inflammatory response, increased periodontal destruction and alveolar bone resorption, and some mechanisms potentially involved in this response have been proposed. The renin-angiotensin system (RAS) regulates several cardiocirculatory parameters, but in addition to its classic role, local renin-angiotensin systems, already described in different tissues including periodontal tissues, have been associated with inflammation and bone metabolism. Type 1 angiotensin II receptor antagonists is one of the most clinically used antihypertensive drug, and among the examples, telmisartan (TELM) attracts attention for its high selectivity, lipophilicity, long half-life, and for being the only in this class with partial agonist activity on PPAR-³ (Peroxisome Proliferator-Activated Gamma Receptor). Previous results from our laboratory showed a significant protective role of telmisartan in the local bone consequences of PD in hypertensive animals, being able to modulate the expression of different bone metabolism markers. MicroRNAs (miRs) are small non-coding interfering RNAs, capable of regulating the expression and translation of different targets and have been drawing attention since their discovery as an important mechanism for epigenetic regulation of physiological and pathological responses. Several studies have focused their efforts on the discovery of potential miRs involved with inflammatory responses, bone loss disorders and systemic diseases. In the present study, we aim to evaluate the role of miRs in PD-induced local bone alterations in an animal model of hypertension and its relationship with local RAS. Normotensive (Wistar rats) and hypertensive animals (SHR) with experimentally-induced PD (bilateral ligature of the first lower first molars, maintained for 15 days), and treated with TELM, will be used to evaluate the differential expression of microRNAs (array) in the alveolar bone, with subsequent in vitro functional studies of the major hits (up-regulated or down-regulated miRs) in alveolar bone-derived osteoblasts and bone marrow derived-osteoclasts by miRs inhibitors or mimics transfection. We intend to better understand the role of miRs in PD-induced local bone consequences in normotensive and hypertensive animals, and their relationship with local RAS, as these are important mechanisms, not yet fully understood. (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)

BRITO, VICTOR GUSTAVO BALERA; PATROCINIO, MARIANA SOUSA; DE SOUSA, MARIA CAROLINA LINJARDI; BARRETO, AYNA EMANUELLI ALVES; FRASNELLI, SABRINA CRUZ TFAILE; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; OLIVEIRA, SANDRA HELENA PENHA. Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease. FRONTIERS IN PHARMACOLOGY, v. 11, NOV 11 2020. (17/02271-2, 18/23676-3, 17/05873-3, 17/07095-8, 15/03965-2)

BRITO, VICTOR GUSTAVO BALERA; PATROCINIO, MARIANA SOUSA; BARRETO, AYNA EMANUELLI ALVES; FRASNELLI, SABRINA CRUZ TFAILE; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; OLIVEIRA, SANDRA HELENA PENHA. Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats. European Journal of Pharmacology, v. 912, DEC 5 2021. (17/02271-2, 15/03965-2, 17/05873-3, 18/23676-3)

BALERA BRITO, VICTOR GUSTAVO; PATROCINIO, MARIANA SOUSA; LINJARDI SOUSA, MARIA CAROLINA; ALVES BARRETO, AYNA EMANUELLI; TFAILE FRASNELLI, SABRINA CRUZ; LARA, VANESSA SOARES; SANTOS, CARLOS FERREIRA; PENHA OLIVEIRA, SANDRA HELENA. Mast cells contribute to alveolar bone loss in Spontaneously Hypertensive Rats with periodontal disease regulating cytokines production. PLoS One, v. 16, n. 3, MAR 4 2021. (18/23676-3, 17/05873-3, 17/07095-8, 17/02271-2, 15/03965-2)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BRITO, Victor Gustavo Balera. Mechanisms associated to the periodontal disease-induced alveolar bone loss in spontaneously hypertensive rats: Role of the renin-angiotensin system and microRNAs. 2023. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba Araçatuba.