Effect of celastrol on bone structure and mechanics in arthritic rats
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/54371 |
Resumo: | © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
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Effect of celastrol on bone structure and mechanics in arthritic ratsAdjuvant-induced arthritisBone lossCelastrolInflammationRheumatoid arthritis© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/Objective: Rheumatoid arthritis (RA) is characterised by chronic inflammation leading to articular bone and cartilage damage. Despite recent progress in RA management, adverse effects, lack of efficacy and economic barriers to treatment access still limit therapeutic success. Therefore, safer and less expensive treatments that control inflammation and bone resorption are needed. We have previously shown that celastrol is a candidate for RA treatment. We have observed that it inhibits both interleukin (IL)-1β and tumor necrosis factor (TNF) in vitro, and that it has anti-inflammatory properties and ability to decrease synovial CD68+ macrophages in vivo. Herein our goal was to evaluate the effect of celastrol in local and systemic bone loss. Methods: Celastrol was administrated intraperitoneally at a dose of 1 µg/g/day to female Wistar adjuvant-induced arthritic rats. Rats were sacrificed after 22 days of disease progression, and blood, femurs, tibiae and paw samples were collected for bone remodelling markers quantification, 3-point bending test, micro-CT analysis, nanoindentation and Fourier transform infrared spectroscopy measurements, and immunohistochemical evaluation. Results: We have observed that celastrol preserved articular structures and decreased the number of osteoclasts and osteoblasts present in arthritic joints. Moreover, celastrol reduced tartrate-resistant acid phosphatase 5b, procollagen type 1 amino-terminal propeptide and C terminal crosslinked telopeptide of type II collagen serum levels. Importantly, celastrol prevented bone loss and bone microarchitecture degradation. Celastrol also preserved bone nanoproperties and mineral content. Additionally, animals treated with celastrol had less fragile bones, as depicted by an increase in maximum load and yield displacement. Conclusions: These results suggest that celastrol reduces both bone resorption and cartilage degradation, and preserves bone structural properties.BMJ Publishing GroupRepositório da Universidade de LisboaCascao, RitaVidal, BrunoJalmari Finnilä, Mikko ArttuLopes, InêsTeixeira, Rui LourençoSaarakkala, SimoMoita, Luis FerreiraFonseca, João Eurico2022-09-08T11:13:51Z20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54371engRMD Open. 2017 Sep 14;3(2):e00043810.1136/rmdopen-2017-0004382056-5933info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T17:00:10Zoai:repositorio.ul.pt:10451/54371Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:04:54.377829Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Effect of celastrol on bone structure and mechanics in arthritic rats |
title |
Effect of celastrol on bone structure and mechanics in arthritic rats |
spellingShingle |
Effect of celastrol on bone structure and mechanics in arthritic rats Cascao, Rita Adjuvant-induced arthritis Bone loss Celastrol Inflammation Rheumatoid arthritis |
title_short |
Effect of celastrol on bone structure and mechanics in arthritic rats |
title_full |
Effect of celastrol on bone structure and mechanics in arthritic rats |
title_fullStr |
Effect of celastrol on bone structure and mechanics in arthritic rats |
title_full_unstemmed |
Effect of celastrol on bone structure and mechanics in arthritic rats |
title_sort |
Effect of celastrol on bone structure and mechanics in arthritic rats |
author |
Cascao, Rita |
author_facet |
Cascao, Rita Vidal, Bruno Jalmari Finnilä, Mikko Arttu Lopes, Inês Teixeira, Rui Lourenço Saarakkala, Simo Moita, Luis Ferreira Fonseca, João Eurico |
author_role |
author |
author2 |
Vidal, Bruno Jalmari Finnilä, Mikko Arttu Lopes, Inês Teixeira, Rui Lourenço Saarakkala, Simo Moita, Luis Ferreira Fonseca, João Eurico |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Cascao, Rita Vidal, Bruno Jalmari Finnilä, Mikko Arttu Lopes, Inês Teixeira, Rui Lourenço Saarakkala, Simo Moita, Luis Ferreira Fonseca, João Eurico |
dc.subject.por.fl_str_mv |
Adjuvant-induced arthritis Bone loss Celastrol Inflammation Rheumatoid arthritis |
topic |
Adjuvant-induced arthritis Bone loss Celastrol Inflammation Rheumatoid arthritis |
description |
© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017 2017-01-01T00:00:00Z 2022-09-08T11:13:51Z |
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://hdl.handle.net/10451/54371 |
url |
http://hdl.handle.net/10451/54371 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
RMD Open. 2017 Sep 14;3(2):e000438 10.1136/rmdopen-2017-000438 2056-5933 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
BMJ Publishing Group |
publisher.none.fl_str_mv |
BMJ Publishing Group |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134600421703680 |