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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 11, NOV 11 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 17/02271-2 - O papel do Telmisartan na diferenciação osteoblástica em animais espontaneamente hipertensos
• Beneficiário: Mariana Sousa Patrocinio
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 18/23676-3 - Participação dos microRNAs nas alterações ósseas locais induzidas pela doença periodontal e pelo sistema renina-angiotensina local em ratos espontaneamente hipertensos
• Beneficiário: Victor Gustavo Balera Brito
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 17/05873-3 - Análise in vitro do papel dos mastócitos e do sistema renina-angiotensina sobre osteoblastos e osteoclastos de animais espontaneamente hipertensos
• Beneficiário: Sabrina Cruz Tfaile Frasnelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/07095-8 - Papel dos mastócitos sobre a diferenciação osteogênica in vitro de células mesenquimais estromais da medula óssea de camundongos
• Beneficiário: Maria Carolina Linjardi de Sousa
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 15/03965-2 - Papel do sistema renina-angiotensina em diferentes modelos inflamatórios orais: uma abordagem interdisciplinar experimental e clínica
• Beneficiário: Carlos Ferreira dos Santos
• Modalidade de apoio: Auxílio à Pesquisa - Temático