| Grant number: | 11/22548-2 |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| Start date: | August 01, 2012 |
| End date: | September 30, 2016 |
| Field of knowledge: | Health Sciences - Medicine - Surgery |
| Principal Investigator: | Mariana Ferreira Leal |
| Grantee: | Mariana Ferreira Leal |
| Host Institution: | Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil |
| City of the host institution: | São Paulo |
| Associated researchers: | Marilia de Arruda Cardoso Smith ; Moises Cohen ; Rommel Mario Rodríguez Burbano ; Síntia Iole Nogueira Belangero |
| Associated scholarship(s): | 12/14768-5 - Nontraumatic orthopedic conditions of shoulder: genetic and molecular aspects, BP.JP |
Abstract
The shoulder is the third most common site of musculoskeletal disease after the spine and the knee. Rotator cuff tear and adhesive capsulitis, also known as "frozen shoulder", are among the most common and debilitating conditions of the shoulder. Although both diseases present a genetic component, the etiology of these diseases are still unknown. It has been proposed that extracellular matrix alterations may be initiated in tendon cells, as well as possibly in the capsule, and may lead to cell proliferation, migration, apoptosis and morphogenesis. An altered balance between extracellular matrix synthesis and degradation may have a role in tendon degeneration and, then, in rotator cuff tear and in the fibrotic process observed in adhesive capsulitis. The present project aims to identify polymorphisms of gene involved, mainly, in the structure and extracellular matrix modelling of tendon and capsule that are associated with the risk of rotator cuff tear and adhesive capsulitis. The expression of genes related to these processes will be evaluated in tissue samples of rotator cuff with and without lesion. To elucidate the transcriptional mechanism control, the DNA methylation pattern and frequency of some of these genes - MMP2, MMP3, MMP9, MMP13, TIMP2 e TIMP3 - and the expression of miR-29b and miR-181a microRNAs will be determined in these tissues. The investigation of genetic, transcriptional and epigenetic mechanisms involved mainly in the extracellular matrix modelling may help in the improvement of prognosis determination and of patient management, as well as the identification of possible targets for new drugs for rotator cuff tear and adhesive capsulitis treatment. This study will generate new biological information that will allow the better understanding of etiopathology and physiology of both conditions with possible medicine application. (AU)
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