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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 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. Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Patol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Ortopedia & Traumatol, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Disciplina Genet, Dept Morfol & Genet, Sao Paulo, SP, Brazil Univ Fed Sao Paulo, Dept Patol, Sao Paulo, SP, Brazil FAPESP: 2011/22548-2 FAPESP: 2012/14768-5 FAPESP: 2016/01392-8 FAPESP: 2016/15785-1 FAPESP: 2013/10691-0 FAPESP: 2013/10791-5 Web of Science

The Down Syndrome (DS) is a chromosomal disease characterized by expression of gene’s copy presents in chromosome 21 in triplicate. Is estimable that the incidence of DS is in the order of 1 in each 600/800 newborn babies and an average with 8000 new cases in Brazil. With basis in this information is verified that the continual need to know the natured of the individuals with Down syndrome as well the advances obtained by the science which is contributing for a larger extension in their lives. This article will expose some molecular mechanisms of DS, genetic and physiologic interactions that result in physical characters, news studies about the pre-natal diagnostic methods, therapies and treatments, besides the questions involving the social inclusion of the people with DS.