Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears

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Leal, Mariana Ferreira ; dos Santos, Leonardo Caires ; de Oliveira, Adrielle Martins ; Belangero, Paulo Santoro ; Figueiredo, Eduardo Antonio ; Cohen, Carina ; Alves, Felipe de Seixas ; Yanaguizawa, Wania Hiromi ; Andreoli, Carlos Vicente ; Pochini, Alberto de Castro ; Ejnisman, Benno ; Smith, Marilia Cardoso ; de Seixas Alves, Maria Teresa ; Cohen, Moises

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 12, n. 9 SEP 13 2017.
• Citações Web of Science: 4

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. (AU)

• Processo FAPESP: 13/10691-0 - Análise histológica e da expressão proteica de colágenos em lesão do ligamento cruzado anterior
• Beneficiário: Felipe de Seixas Alves
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 11/22548-2 - Afecções ortopédicas não traumáticas de ombro: aspectos genéticos e moleculares
• Beneficiário: Mariana Ferreira Leal
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 12/14768-5 - Afecções ortopédicas não traumáticas de ombro: aspectos genéticos e moleculares
• Beneficiário: Mariana Ferreira Leal
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 16/01392-8 - Processamento de amostras biológicas e analise da expressão e de variantes polimórficas de genes envolvidos no modelamento da matriz extracelular de tendões na lesão do manguito rotador
• Beneficiário: Adrielle Martins de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 13/10791-5 - Análise histológica e da imunorreatividade de proteínas de matriz extracelular em lesões ortopédicas relacionadas à prática esportiva
• Beneficiário: Wânia Hiromi Yanaguizawa
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
• Processo FAPESP: 16/15785-1 - "análise da expressão de mir-29b em lesões traumáticas do joelho"
• Beneficiário: Adrielle Martins de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico