Telmisartan Prevents Alveolar Bone Loss by Decreasing the Expression of Osteoclasts Markers in Hypertensive Rats With Periodontal Disease
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
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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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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1799965006986477568 |