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

Detalhes bibliográficos
Autor(a) principal: Brito, Victor Gustavo Balera [UNESP]
Data de Publicação: 2020
Outros Autores: Patrocinio, Mariana Sousa [UNESP], de Sousa, Maria Carolina Linjardi [UNESP], Barreto, Ayná Emanuelli Alves [UNESP], Frasnelli, Sabrina Cruz Tfaile [UNESP], Lara, Vanessa Soares, Santos, Carlos Ferreira, Oliveira, Sandra Helena Penha [UNESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.3389/fphar.2020.579926
http://hdl.handle.net/11449/207899
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-α), interleukin-1β (IL-1β), 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-α, IL-1β, 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.
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spelling Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal DiseaseAT1 blockerbone metabolismcytokinesosteobalstosteoclastperiodontal disease 4spontaneous hypertensive ratstelmisartanPeriodontal 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-α), interleukin-1β (IL-1β), 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-α, IL-1β, 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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Department of Basic Sciences School of Dentistry São Paulo State University (UNESP)Multicenter Postgraduate Program in Physiological Sciences Brazilian Society of Physiology School of Dentistry São Paulo State University (UNESP)Department of Stomatology Bauru School of Dentistry University of São PauloDepartment of Biological Science Bauru School of Dentistry University of São PauloDepartment of Basic Sciences School of Dentistry São Paulo State University (UNESP)Multicenter Postgraduate Program in Physiological Sciences Brazilian Society of Physiology School of Dentistry São Paulo State University (UNESP)FAPESP: 2015/03965-2FAPESP: 2017/02271-2FAPESP: 2017/05873-3FAPESP: 2017/07095-8Universidade Estadual Paulista (Unesp)Universidade de São Paulo (USP)Brito, Victor Gustavo Balera [UNESP]Patrocinio, Mariana Sousa [UNESP]de Sousa, Maria Carolina Linjardi [UNESP]Barreto, Ayná Emanuelli Alves [UNESP]Frasnelli, Sabrina Cruz Tfaile [UNESP]Lara, Vanessa SoaresSantos, Carlos FerreiraOliveira, Sandra Helena Penha [UNESP]2021-06-25T11:02:57Z2021-06-25T11:02:57Z2020-11-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.3389/fphar.2020.579926Frontiers in Pharmacology, v. 11.1663-9812http://hdl.handle.net/11449/20789910.3389/fphar.2020.5799262-s2.0-85096791364Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers in Pharmacologyinfo:eu-repo/semantics/openAccess2024-04-23T15:23:29Zoai:repositorio.unesp.br:11449/207899Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-23T15:23:29Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
title Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
spellingShingle Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
Brito, Victor Gustavo Balera [UNESP]
AT1 blocker
bone metabolism
cytokines
osteobalst
osteoclast
periodontal disease 4
spontaneous hypertensive rats
telmisartan
title_short Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
title_full Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
title_fullStr Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
title_full_unstemmed Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
title_sort Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
author Brito, Victor Gustavo Balera [UNESP]
author_facet Brito, Victor Gustavo Balera [UNESP]
Patrocinio, Mariana Sousa [UNESP]
de Sousa, Maria Carolina Linjardi [UNESP]
Barreto, Ayná Emanuelli Alves [UNESP]
Frasnelli, Sabrina Cruz Tfaile [UNESP]
Lara, Vanessa Soares
Santos, Carlos Ferreira
Oliveira, Sandra Helena Penha [UNESP]
author_role author
author2 Patrocinio, Mariana Sousa [UNESP]
de Sousa, Maria Carolina Linjardi [UNESP]
Barreto, Ayná Emanuelli Alves [UNESP]
Frasnelli, Sabrina Cruz Tfaile [UNESP]
Lara, Vanessa Soares
Santos, Carlos Ferreira
Oliveira, Sandra Helena Penha [UNESP]
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade Estadual Paulista (Unesp)
Universidade de São Paulo (USP)
dc.contributor.author.fl_str_mv Brito, Victor Gustavo Balera [UNESP]
Patrocinio, Mariana Sousa [UNESP]
de Sousa, Maria Carolina Linjardi [UNESP]
Barreto, Ayná Emanuelli Alves [UNESP]
Frasnelli, Sabrina Cruz Tfaile [UNESP]
Lara, Vanessa Soares
Santos, Carlos Ferreira
Oliveira, Sandra Helena Penha [UNESP]
dc.subject.por.fl_str_mv AT1 blocker
bone metabolism
cytokines
osteobalst
osteoclast
periodontal disease 4
spontaneous hypertensive rats
telmisartan
topic AT1 blocker
bone metabolism
cytokines
osteobalst
osteoclast
periodontal disease 4
spontaneous hypertensive rats
telmisartan
description 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-α), interleukin-1β (IL-1β), 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-α, IL-1β, 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.
publishDate 2020
dc.date.none.fl_str_mv 2020-11-11
2021-06-25T11:02:57Z
2021-06-25T11:02:57Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.3389/fphar.2020.579926
Frontiers in Pharmacology, v. 11.
1663-9812
http://hdl.handle.net/11449/207899
10.3389/fphar.2020.579926
2-s2.0-85096791364
url http://dx.doi.org/10.3389/fphar.2020.579926
http://hdl.handle.net/11449/207899
identifier_str_mv Frontiers in Pharmacology, v. 11.
1663-9812
10.3389/fphar.2020.579926
2-s2.0-85096791364
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Frontiers in Pharmacology
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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