Progressive scoliosis deformity in intervertebral disc

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DESCRIPTION (provided by applicant): Progressive spinal deformities (notably scoliosis and spondylolisthesis) progress most rapidly during the adolescent growth spurt. In scoliosis (including neuromuscular, congenital and idiopathic forms) this progression involves increasing wedging deformity of the vertebrae and discs in the coronal plane, together with lesser magnitudes of deformity in other planes. While it appears that mechanically modulated endochondral growth is responsible in large part for the progressive vertebral wedging, the mechanism by which intervertebral discs become increasingly deformed is largely unknown and probably very different, since there is minimal growth of intervertebral discs accompanying adolescent vertebral growth. The proposed studies will determine how intervertebral discs respond to the altered stress that occurs in a skeletally immature spine with scoliosis. A skeletally immature rat tail model that has demonstrated vertebral wedging as seen in scoliosis will be extended to determine the changes in the intervertebral disc with angulation deformity and compressive loading. Three permutations of sustained compression and sustained angulation for up to 5 weeks will be compared. Loaded and/or deformed and adjacent control discs will be measured to determine morphological, structural and mechanical changes, annulus tissue composition (including convex and concave sides), protein synthesis and cellularity. Protein synthesis will be evaluated along with gene expression for major proteins involved in synthesis and degradation of disc tissue. The findings will be interpreted with reference to the overall hypothesis that the intervertebral disc component of scoliosis progression results from mechanically-mediated remodelling and degeneration of the intervertebral disc on the concave side, which is chronically more heavily loaded. The major challenges in designing early interventions clinically to prevent scoliosis progression are the unknown mechanisms of scoliosis progression during adolescence and absence of accurate tests to identify potentially progressive deformities (prognosis). The proposed work provide improved understanding of deformity progression to permit design of novel therapeutic approaches to restore symmetrical growth of the spine. These approaches may include improvements in brace design, new possibilities for muscle rehabilitation, and surgical procedures aimed at early, minimally invasive modification of spinal growth.