AUTHOR=Brito Victor Gustavo Balera , Patrocinio Mariana Sousa , Linjardi Maria Carolina , Barreto Ayná Emanuelli Alves , Frasnelli Sabrina CT , Lara Vanessa , Santos Carlos Ferreira , Oliveira Sandra Helena Penha 

TITLE=Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.579926

DOI=10.3389/fphar.2020.579926

ISSN=1663-9812

ABSTRACT=Periodontal disease (PD) is a prevalent inflammatory disease with the most severe consequence being the loss of the alveolar bone and teeth. We therefore aimed to evaluate the effects of telmisartan (TELM), an angiotensin II type 1 receptor (Agtr1) antagonist, on the PD-induced loss of alveolar bone, in Wistar (W) and spontaneous hypertensive rats (SHRs). PD was induced by ligating the lower first molars with silk, and 10 mg/kg TELM was concomitantly administered for 15 days. The hemimandibles were subjected to microtomography. ELISA was used for detecting tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of RAS (Agt, Ace, Agt1r, and Agt2r), and bone markers (Runx2, Osx, Catnb, Alp, Col1a1, Opn, Ocn, Bsp, Bmp2, Trap, Rank, Rankl, CtsK, Mmp-2, Mmp-9, and osteoclast-associated receptor (Oscar)). The SHR+PD group showed greater alveolar bone loss than the W+PD group. Alveolar bone loss was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-α, IL-1β, and CXCL3 in the SHR group. The expression of angiotensin increased in the groups with PD, while the expression of Agtr2 reduced. TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in both the SHRs and W rats. PD did not induce major changes in the expression of bone formation markers, with the exception of the expression of Alp, which decreased in the W+PD and SHR+PD groups. The expression of the bone resorption markers, Mmp9, Ctsk, and Vtn, was higher in the SHR+PD group, compared to the respective control groups and the W+PD group. However, TELM attenuated these changes and increased the expression of Runx2 and Alp. Our study suggested that TELM has a protective effect on the progression of PD, especially in hypertensive animals, as evaluated by the resorption of the lower alveolar bone. This can be partly explained by the modulation in the expression of Angiotensin II receptors (AT1R and AT2R), the reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the markers of bone formation.