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Nontraumatic orthopedic conditions of shoulder: genetic and molecular aspects

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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Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
FIGUEIREDO, EDUARDO A.; LOYOLA, LEONOR CASILLA; BELANGERO, PAULO S.; CAMPOS RIBEIRO-DOS-SANTOS, ANDREA KELY; BATISTA SANTOS, SIDNEY EMANUEL; COHEN, CARINA; WAJNSZTEJN, ANDRE; DE OLIVEIRA, ADRIELLE MARTINS; SMITH, MARILIA C.; POCHINI, ALBERTO DE CASTRO; ANDREOLI, CARLOS V.; EJNISMAN, BENNO; COHEN, MOISES; LEAL, MARIANA F. Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis. JOURNAL OF ORTHOPAEDIC RESEARCH, v. 38, n. 1, SI, p. 192-201, JAN 2020. Web of Science Citations: 3.
COHEN, CARINA; LEAL, MARIANA F.; LOYOLA, LEONOR C.; SANTOS, SIDNEY E. B.; RIBEIRO-DOS-SANTOS, ANDREA K. C.; BELANGERO, PAULO S.; FIGUEIREDO, EDUARDO A.; WAJNSZTEJN, ANDRE; DE OLIVEIRA, ADRIELLE M.; SMITH, MARILIA C.; ANDREOLI, CARLOS V.; POCHINI, ALBERTO DE CASTRO; COHEN, MOISES; EJNISMAN, BENNO; FALOPPA, FLAVIO. Genetic variants involved in extracellular matrix homeostasis play a role in the susceptibility to frozen shoulder: A case-control study. JOURNAL OF ORTHOPAEDIC RESEARCH, v. 37, n. 4, p. 948-956, APR 2019. Web of Science Citations: 1.
BELANGERO, PAULO SANTORO; FIGUEIREDO, EDUARDO ANTONIO; COHEN, CARINA; ALVES, FELIPE DE SEIXAS; YANAGUIZAWA, WANIA HIROMI; SMITH, MARILIA CARDOSO; ANDREOLI, CARLOS VICENTE; POCHINI, ALBERTO DE CASTRO; DE SEIXAS ALVES, MARIA TERESA; EJNISMAN, BENNO; COHEN, MOISES; LEAL, MARIANA FERREIRA. Changes in the expression of matrix extracellular genes and TGFB family members in rotator cuff tears. JOURNAL OF ORTHOPAEDIC RESEARCH, v. 36, n. 9, p. 2542-2553, SEP 2018. Web of Science Citations: 0.
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. Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears. PLoS One, v. 12, n. 9 SEP 13 2017. Web of Science Citations: 4.
GIGEK, CAROLINA OLIVEIRA; CALCAGNO, DANIELLE QUEIROZ; RASMUSSEN, LUCAS TREVIZANI; SANTOS, LEONARDO CAIRES; LEAL, MARIANA FERREIRA; WISNIESKI, FERNANDA; BURBANO, ROMMEL RODRIGUEZ; LOURENCO, LAERCIO GOMES; LOPES-FILHO, GASPAR JESUS; CARDOSO SMITH, MARILIA ARRUDA. Genetic variants in gastric cancer: Risks and clinical implications. Experimental and Molecular Pathology, v. 103, n. 1, p. 101-111, AUG 2017. Web of Science Citations: 14.

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