Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | https://repositorio.unifesp.br/handle/11600/57359 https://dx.doi.org/10.1371/journal.pone.0184141 |
Resumo: | Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears. |
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Leal, Mariana Ferreira [UNIFESP]Santos, Leonardo Caires dos [UNIFESP]Oliveira, Adrielle Martins de [UNIFESP]Belangero, Paulo Santoro [UNIFESP]Figueiredo, Eduardo Antonio [UNIFESP]Cohen, Carina [UNIFESP]Alves, Felipe de Seixas [UNIFESP]Yanaguizawa, Wania Hiromi [UNIFESP]Andreoli, Carlos Vicente [UNIFESP]Pochini, Alberto de Castro [UNIFESP]Ejnisman, Benno [UNIFESP]Smith, Marilia Cardoso [UNIFESP]Alves, Maria Teresa de Seixas [UNIFESP]Cohen, Moises [UNIFESP]2020-08-04T13:40:12Z2020-08-04T13:40:12Z2017Plos One. San Francisco, v. 12, n. 9, p. -, 2017.1932-6203https://repositorio.unifesp.br/handle/11600/57359https://dx.doi.org/10.1371/journal.pone.0184141WOS000410669200028.pdf10.1371/journal.pone.0184141WOS:000410669200028Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Patol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Patol, Sao Paulo, SP, BrazilFAPESP: 2011/22548-2FAPESP: 2012/14768-5FAPESP: 2016/01392-8FAPESP: 2016/15785-1FAPESP: 2013/10691-0FAPESP: 2013/10791-5Web of Science-engPublic Library SciencePlos OneEpigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tearsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleSan Francisco129info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000410669200028.pdfapplication/pdf2365192${dspace.ui.url}/bitstream/11600/57359/1/WOS000410669200028.pdf75ee14d625fbd1ff4e2f546347c99dcfMD51open accessTEXTWOS000410669200028.pdf.txtWOS000410669200028.pdf.txtExtracted texttext/plain59259${dspace.ui.url}/bitstream/11600/57359/2/WOS000410669200028.pdf.txt8e6247d87ee8223a5c4d5cd242d9e50cMD52open accessTHUMBNAILWOS000410669200028.pdf.jpgWOS000410669200028.pdf.jpgIM Thumbnailimage/jpeg7890${dspace.ui.url}/bitstream/11600/57359/4/WOS000410669200028.pdf.jpg6f6abbb133533c04f7ea31992a090f81MD54open access11600/573592022-07-31 21:26:08.684open accessoai:repositorio.unifesp.br:11600/57359Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T00:26:08Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
title |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
spellingShingle |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears Leal, Mariana Ferreira [UNIFESP] |
title_short |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
title_full |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
title_fullStr |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
title_full_unstemmed |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
title_sort |
Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears |
author |
Leal, Mariana Ferreira [UNIFESP] |
author_facet |
Leal, Mariana Ferreira [UNIFESP] Santos, Leonardo Caires dos [UNIFESP] Oliveira, Adrielle Martins de [UNIFESP] Belangero, Paulo Santoro [UNIFESP] Figueiredo, Eduardo Antonio [UNIFESP] Cohen, Carina [UNIFESP] Alves, Felipe de Seixas [UNIFESP] Yanaguizawa, Wania Hiromi [UNIFESP] Andreoli, Carlos Vicente [UNIFESP] Pochini, Alberto de Castro [UNIFESP] Ejnisman, Benno [UNIFESP] Smith, Marilia Cardoso [UNIFESP] Alves, Maria Teresa de Seixas [UNIFESP] Cohen, Moises [UNIFESP] |
author_role |
author |
author2 |
Santos, Leonardo Caires dos [UNIFESP] Oliveira, Adrielle Martins de [UNIFESP] Belangero, Paulo Santoro [UNIFESP] Figueiredo, Eduardo Antonio [UNIFESP] Cohen, Carina [UNIFESP] Alves, Felipe de Seixas [UNIFESP] Yanaguizawa, Wania Hiromi [UNIFESP] Andreoli, Carlos Vicente [UNIFESP] Pochini, Alberto de Castro [UNIFESP] Ejnisman, Benno [UNIFESP] Smith, Marilia Cardoso [UNIFESP] Alves, Maria Teresa de Seixas [UNIFESP] Cohen, Moises [UNIFESP] |
author2_role |
author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Leal, Mariana Ferreira [UNIFESP] Santos, Leonardo Caires dos [UNIFESP] Oliveira, Adrielle Martins de [UNIFESP] Belangero, Paulo Santoro [UNIFESP] Figueiredo, Eduardo Antonio [UNIFESP] Cohen, Carina [UNIFESP] Alves, Felipe de Seixas [UNIFESP] Yanaguizawa, Wania Hiromi [UNIFESP] Andreoli, Carlos Vicente [UNIFESP] Pochini, Alberto de Castro [UNIFESP] Ejnisman, Benno [UNIFESP] Smith, Marilia Cardoso [UNIFESP] Alves, Maria Teresa de Seixas [UNIFESP] Cohen, Moises [UNIFESP] |
description |
Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2020-08-04T13:40:12Z |
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2020-08-04T13:40:12Z |
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article |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco, v. 12, n. 9, p. -, 2017. |
dc.identifier.uri.fl_str_mv |
https://repositorio.unifesp.br/handle/11600/57359 https://dx.doi.org/10.1371/journal.pone.0184141 |
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1932-6203 |
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WOS000410669200028.pdf |
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10.1371/journal.pone.0184141 |
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Plos One. San Francisco, v. 12, n. 9, p. -, 2017. 1932-6203 WOS000410669200028.pdf 10.1371/journal.pone.0184141 WOS:000410669200028 |
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https://repositorio.unifesp.br/handle/11600/57359 https://dx.doi.org/10.1371/journal.pone.0184141 |
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