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

Author(s)

Brito, Victor Gustavo Balera ^{[1, 2]} ; Patrocinio, Mariana Sousa ^{[1, 2]} ; de Sousa, Maria Carolina Linjardi ^{[1, 2]} ; Barreto, Ayna Emanuelli Alves ^{[1, 2]} ; Frasnelli, Sabrina Cruz Tfaile ^{[1, 2]} ; Lara, Vanessa Soares ^[3] ; Santos, Carlos Ferreira ^[4] ; Oliveira, Sandra Helena Penha ^{[1, 2]}

Affiliation

^[1] Sao Paulo State Univ UNESP, Sch Dent, Dept Basic Sci, Aracatuba - Brazil

^[2] Sao Paulo State Univ UNESP, Sch Dent, Multictr Postgrad Program Physiol Sci, Brazilian Soc Physiol, Aracatuba - Brazil

^[3] Univ Sao Paulo, Bauru Sch Dent, Dept Stomatol, Bauru, SP - Brazil

^[4] Univ Sao Paulo, Bauru Sch Dent, Dept Biol Sci, Bauru, SP - Brazil

• Document type: Journal article
• Source: FRONTIERS IN PHARMACOLOGY; v. 11, NOV 11 2020.
• Web of Science Citations: 0

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 alveolar bone loss, 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-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), CXCL3, and CCL2, while qRT-PCR was used for analyzing expression of components of renin-angiotensin system (RAS) (Agt, Ace, Agt1r, Agt2r, Ace2, and Masr), 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, what was significantly inhibited by treatment with TELM, especially in the SHR group. Additionally, TELM reduced the production of TNF-alpha, IL-1 beta, and CXCL3 in the SHR group. The expression of Agt increased in the groups with PD, while Agtr2 reduced, and TELM reduced the expression of Agtr1 and increased the expression of Agtr2, in W and SHRs. PD did not induce major changes in the expression of bone formation markers, except for the expression of Alp, which decreased in the PD groups. The bone resorption markers expression, Mmp9, Ctsk, and Vtn, was higher in the SHR + PD group, compared to the respective control and 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), reduced production of inflammatory mediators, the reduced expression of resorption markers, and the increased expression of the bone formation markers. (AU)

• FAPESP's process: 17/02271-2 - The role of Telmisartan in osteoblastic differentiation in spontaneously hypertensive rats
• Grantee: Mariana Sousa Patrocinio
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 18/23676-3 - MicroRNAs role in bone impairment induced by periodontal disease and the local renin-angiotensin system in spontaneous hypertensive rats
• Grantee: Victor Gustavo Balera Brito
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/05873-3 - In vitro analysis of mast cells and renin-angiotensin system role of spontaneously hypertensive animals osteoblasts and osteoclasts
• Grantee: Sabrina Cruz Tfaile Frasnelli
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 17/07095-8 - The role of mast cells upon the in vitro osteogenic differentiation of the mesenchymal stromal cells from the bone marrow of mice
• Grantee: Maria Carolina Linjardi de Sousa
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/03965-2 - Role of the renin-angiotensin system in different oral inflammatory models: an experimental interdisciplinary and clinical approach
• Grantee: Carlos Ferreira dos Santos
• Support type: Research Projects - Thematic Grants