Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears

Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears

Author Leal, Mariana Ferreira Autor UNIFESP Google Scholar
dos Santos, Leonardo Caires Autor UNIFESP Google Scholar
de Oliveira, Adrielle Martins Autor UNIFESP Google Scholar
Belangero, Paulo Santoro Autor UNIFESP Google Scholar
Figueiredo, Eduardo Antonio Autor UNIFESP Google Scholar
Cohen, Carina Autor UNIFESP Google Scholar
Alves, Felipe de Seixas Autor UNIFESP Google Scholar
Yanaguizawa, Wania Hiromi Autor UNIFESP Google Scholar
Andreoli, Carlos Vicente Autor UNIFESP Google Scholar
Pochini, Alberto de Castro Autor UNIFESP Google Scholar
Ejnisman, Benno Autor UNIFESP Google Scholar
Smith, Marilia Cardoso Autor UNIFESP Google Scholar
de Seixas Alves, Maria Teresa Autor UNIFESP Google Scholar
Cohen, Moises Autor UNIFESP Google Scholar
Abstract 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.
xmlui.dri2xhtml.METS-1.0.item-coverage San Francisco
Language English
Sponsor Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
Grant number FAPESP: 2011/22548-2
FAPESP: 2012/14768-5
FAPESP: 2016/01392-8
FAPESP: 2016/15785-1
FAPESP: 2013/10691-0
FAPESP: 2013/10791-5
Date 2017
Published in Plos One. San Francisco, v. 12, n. 9, p. -, 2017.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent -
Origin http://dx.doi.org/10.1371/journal.pone.0184141
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000410669200028
URI https://repositorio.unifesp.br/handle/11600/57359

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