Progressive scoliosis deformity in intervertebral disc

描述（由申请人提供）：进行性脊柱畸形（特别是脊柱侧凸和脊椎前移）在青少年生长突增期进展最快。在脊柱侧凸（包括神经肌肉性、先天性和特发性形式）中，这种进展涉及冠状面中椎骨和椎间盘的楔形畸形增加，以及其他平面中较小程度的畸形。虽然似乎机械调节的软骨内生长在很大程度上是渐进性椎骨楔入的原因，但椎间盘逐渐变形的机制在很大程度上是未知的，并且可能非常不同，因为伴随青少年椎骨生长的椎间盘生长最小。这项研究将确定椎间盘如何对脊柱侧凸的未成熟脊柱中发生的应力变化做出反应。一个未成熟的大鼠尾部模型已经证明了脊柱侧凸中的椎体楔入，该模型将被扩展以确定椎间盘成角畸形和压缩载荷的变化。将比较长达5周的持续加压和持续成角的三种排列。将测量加载和/或变形的和相邻的对照椎间盘，以确定形态、结构和机械变化、瓣环组织组成（包括凸面和凹面）、蛋白质合成和细胞构成。蛋白质合成将沿着参与椎间盘组织合成和降解的主要蛋白质的基因表达进行评估。将参照总体假设来解释这些发现，即脊柱侧凸进展的椎间盘成分是由机械介导的凹面椎间盘重塑和退变引起的，凹面椎间盘长期负荷更重。在临床上设计预防脊柱侧凸进展的早期干预措施的主要挑战是青少年时期脊柱侧凸进展的机制未知，以及缺乏准确的测试来识别潜在的进行性畸形（预后）。建议的工作提供了更好的理解畸形的进展，允许设计新的治疗方法，以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.