Progressive scoliosis deformity in intervertebral disc

描述(申请人提供)：进行性脊柱畸形(尤其是脊柱侧弯和腰椎滑脱)在青春期生长发育期进展最快。在脊柱侧弯(包括神经肌肉型、先天性和特发性)，这一进展涉及椎体和椎间在冠状平面上的楔形畸形增加，以及其他平面上的较小程度的畸形。虽然机械调节的软骨内生长似乎在很大程度上导致了椎体的进行性楔入，但椎间盘变得越来越变形的机制在很大程度上是未知的，可能是非常不同的，因为伴随青少年椎体生长的是椎间盘的微小生长。这项拟议的研究将确定在患有脊柱侧弯的骨骼未成熟脊柱中，椎间盘对改变的应力有何反应。一个骨骼未成熟的大鼠尾巴模型，已经显示了脊柱侧弯中的椎体楔形，将被扩展以确定有角度畸形和压缩负荷的椎间盘的变化。将比较持续加压和持续角度长达5周的三种排列方式。将测量加载的和/或变形的和相邻的对照盘，以确定形态、结构和机械变化、环状组织成分(包括凸面和凹面)、蛋白质合成和细胞密度。蛋白质合成将与参与椎间盘组织合成和降解的主要蛋白质的基因表达一起进行评估。这些发现将参考整体假设来解释，即脊柱侧弯进展的间盘成分是由于机械介导的凹侧间盘的重塑和退变所致，而凹侧的间盘长期负荷更重。在临床上设计早期干预措施以防止脊柱侧弯进展的主要挑战是青春期脊柱侧弯进展的未知机制，以及缺乏准确的测试来识别潜在的进行性畸形(预后)。这项拟议的工作提供了对畸形进展的更好的理解，以允许设计新的治疗方法来恢复脊柱的对称生长。这些方法可能包括改进支具设计，肌肉康复的新可能性，以及旨在早期、微创修改脊柱生长的外科手术。

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.