| Grant number: | 11/18688-3 |
| Support Opportunities: | Regular Research Grants |
| Start date: | February 01, 2012 |
| End date: | January 31, 2014 |
| Field of knowledge: | Biological Sciences - Biochemistry - Molecular Biology |
| Principal Investigator: | Maria Aparecida da Silva Pinhal |
| Grantee: | Maria Aparecida da Silva Pinhal |
| Host Institution: | Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil |
Abstract
The intervertebral disc degenerative process is an aberrant response to progressive structural deficiency. This process occurs as a result of biochemical alterations and can, eventually, develop with age, smoke habit, excessive weight, diabetes or genetic and epigenetic factors. The main alteration in the disease is the progressive loss of proteoglycans, water and collagen of nucleus pulposus extracellular matrix. Other matrix components, such as hyaluronan, interleukins and glucosidases are altered in the degenerative process. Heparanase is an endo-beta-glucuronidase that cleaves extracellular heparan sulfate chains, realeasing growth factors and proteins bound to the extracellular matrix. The enzyme promotes cellular adhesion, migration and invasion and plays important roles in angiogenesis and inflammation. There are two heparanase isoforms: heparanase-1 (HPSE1) and heparanase-2 (HPSE2). Recent study from our group demonstrated the mRNA and protein expressions of both heparanase isoforms in the nucleus pulposus and annulus fibrosus of degenerated intervertebral discs, suggesting a possible role for HPSE1 and HPSE2 in the pathophysiology of the disease. Although intervertebral disc degeneration is a big health problem, the alterations in important matrix components and the inflammation mechanism of the disease are not entirely elucidated. The present study aims to identify molecular alterations in the extracellular matrix and analyze the inflammation mechanism of the intervertebral disc degeneration, comparing groups of patients with the disease, as well as patients with scoliosis, with a group of healthy individuals, all of them in young age and contribute to understand the pathophysiology of the disease. Thus, we intend to analyze the proteoglycan distribution, as well as the distribution of other molecules wich constitute the extracellular matrix, in degenerated intervertebral discs in comparison with healthy discs; characterize the inflammation process of the intervertebral disc degeneration; investigate the presence of genetic mutations and epigenetic alterations in the gene that codes HPSE1 and correlate with the overexpression of the enzyme in patients with disc degeneration and, finally, correlate the epigenetic alterations and possible polymorphisms with the pathophysiology of the intervertebral disc degeneration. (AU)
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