Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats
Autor(a) principal: | |
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Data de Publicação: | 2021 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.ejphar.2021.174609 http://hdl.handle.net/11449/231545 |
Resumo: | Telmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 μM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 μM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation. |
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Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male ratsBone marrow-derived mesenchymal stromal cellHypertensionOsteogenic differentiationSpontaneously hypertensive ratsTelmisartanTelmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 μM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 μM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation.Department of Basic Sciences São Paulo State University (UNESP) School of DentistryMulticenter Postgraduate Program in Physiological Sciences Brazilian Society of Physiology São Paulo State University (UNESP) School of DentistryDepartment of Stomatology Bauru School of Dentistry University of São Paulo (USP)Department of Biological Science Bauru School of Dentistry University of São Paulo (USP)Department of Basic Sciences São Paulo State University (UNESP) School of DentistryMulticenter Postgraduate Program in Physiological Sciences Brazilian Society of Physiology São Paulo State University (UNESP) School of DentistryUniversidade Estadual Paulista (UNESP)Universidade de São Paulo (USP)Balera Brito, Victor Gustavo [UNESP]Patrocinio, Mariana Sousa [UNESP]Alves Barreto, Ayná Emanuelli [UNESP]Tfaile Frasnelli, Sabrina Cruz [UNESP]Lara, Vanessa SoaresSantos, Carlos FerreiraPenha Oliveira, Sandra Helena [UNESP]2022-04-29T08:46:04Z2022-04-29T08:46:04Z2021-12-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.ejphar.2021.174609European Journal of Pharmacology, v. 912.1879-07120014-2999http://hdl.handle.net/11449/23154510.1016/j.ejphar.2021.1746092-s2.0-85118356633Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengEuropean Journal of Pharmacologyinfo:eu-repo/semantics/openAccess2024-04-23T15:22:58Zoai:repositorio.unesp.br:11449/231545Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-04-23T15:22:58Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
title |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
spellingShingle |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats Balera Brito, Victor Gustavo [UNESP] Bone marrow-derived mesenchymal stromal cell Hypertension Osteogenic differentiation Spontaneously hypertensive rats Telmisartan |
title_short |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
title_full |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
title_fullStr |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
title_full_unstemmed |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
title_sort |
Telmisartan impairs the in vitro osteogenic differentiation of mesenchymal stromal cells from spontaneously hypertensive male rats |
author |
Balera Brito, Victor Gustavo [UNESP] |
author_facet |
Balera Brito, Victor Gustavo [UNESP] Patrocinio, Mariana Sousa [UNESP] Alves Barreto, Ayná Emanuelli [UNESP] Tfaile Frasnelli, Sabrina Cruz [UNESP] Lara, Vanessa Soares Santos, Carlos Ferreira Penha Oliveira, Sandra Helena [UNESP] |
author_role |
author |
author2 |
Patrocinio, Mariana Sousa [UNESP] Alves Barreto, Ayná Emanuelli [UNESP] Tfaile Frasnelli, Sabrina Cruz [UNESP] Lara, Vanessa Soares Santos, Carlos Ferreira Penha Oliveira, Sandra Helena [UNESP] |
author2_role |
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 |
Balera Brito, Victor Gustavo [UNESP] Patrocinio, Mariana Sousa [UNESP] Alves Barreto, Ayná Emanuelli [UNESP] Tfaile Frasnelli, Sabrina Cruz [UNESP] Lara, Vanessa Soares Santos, Carlos Ferreira Penha Oliveira, Sandra Helena [UNESP] |
dc.subject.por.fl_str_mv |
Bone marrow-derived mesenchymal stromal cell Hypertension Osteogenic differentiation Spontaneously hypertensive rats Telmisartan |
topic |
Bone marrow-derived mesenchymal stromal cell Hypertension Osteogenic differentiation Spontaneously hypertensive rats Telmisartan |
description |
Telmisartan (TELM) is an angiotensin II (Ang II) type 1 receptor (Agtr1) antagonist, with partial agonism for Pparg, and has been shown to affect bone metabolism. Therefore, the aim of this study was to investigate the effects of TELM in the in vitro osteogenic differentiation of bone marrow-derived mesenchymal stromal cells (BMSC) from spontaneously hypertensive rats (SHRs). BMSC were obtained from male SHR, and the osteogenic medium (OM) was added to the cells concomitantly with TELM (0.005, 0.05, and 0.5 μM). Undifferentiated BMSC, in control medium (CM), showed an increased viability, while the addition of OM reduced this parameter, and TELM did not show cytotoxicity in the concentrations used. BMSC in OM had an alkaline phosphatase (ALP) activity peak at d10, which decreased at d14 and d21, and TELM reduced ALP at d10 in a dose-dependent manner. Mineralization was observed in the OM at d14, which intensified at d21, but was inhibited by TELM. Agtr1b was increased in the OM, and TELM inhibited its expression. TELM reduced Opn, Ocn, and Bsp and increased Pparg expression, and at the higher concentration TELM also increased the expression of adipogenic markers, Fabp4 and Adipoq. In addition, TELM 0.5 μM increased Irs1 and Glut4, insulin and glucose metabolism markers, known to be regulated by Pparg and to be related to adipogenic phenotype. Our data shows that TELM inhibited the osteogenic differentiation and mineralization of SHR BMSC, by favoring an adipogenic prone phenotype due to Pparg upregulation. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-12-05 2022-04-29T08:46:04Z 2022-04-29T08:46:04Z |
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/10.1016/j.ejphar.2021.174609 European Journal of Pharmacology, v. 912. 1879-0712 0014-2999 http://hdl.handle.net/11449/231545 10.1016/j.ejphar.2021.174609 2-s2.0-85118356633 |
url |
http://dx.doi.org/10.1016/j.ejphar.2021.174609 http://hdl.handle.net/11449/231545 |
identifier_str_mv |
European Journal of Pharmacology, v. 912. 1879-0712 0014-2999 10.1016/j.ejphar.2021.174609 2-s2.0-85118356633 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
European Journal of 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 |
|
_version_ |
1799964481896316928 |