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Progressive scoliosis deformity in intervertebral disc

椎间盘进行性脊柱侧凸畸形

基本信息

批准号：
7647095
负责人：
IAN A. STOKES
金额：
$ 31.82万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-01 至 2010-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7647095
关键词：
Adolescence Adolescent Affect Animals Articular Range of Motion Biological Assay Braces-Orthopedic appliances Cellularity Collagen Deformity Diffusion Early treatment Enzymes Gene Expression Growth Harvest Height Human Inorganic Sulfates Intervertebral disc structure Lateral MMP3 gene Measures Mechanics Mediating Messenger RNA Metabolism Modeling Modification Muscle rehabilitation Nutrient Operative Surgical Procedures Permeability Ploidies Polarization Microscopy Proline Protein Biosynthesis Proteins Rattus Research Personnel Reverse Transcriptase Polymerase Chain Reaction Rotation Side Spinal Spondylolisthesis Stress Structure TIMP1 gene TIMP3 gene Tail Testing Time Tissues Unspecified or Sulfate Ion Sulfates Vascular blood supply Vertebral column Water Weight Work X ray diffraction analysis X-Ray Diffraction aggrecan design flexibility improved in vivo inhibitor/antagonist intervertebral disk degeneration mechanical behavior minimally invasive neuromuscular novel therapeutic intervention nutrition outcome forecast prevent progesterone 11-hemisuccinate-(2-iodohistamine)response scoliosis spine bone structure

项目摘要

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.

描述（由申请人提供）：进行性脊柱畸形（特别是脊柱侧弯和脊椎滑脱）在青少年生长突增期间进展最快。在脊柱侧凸（包括神经肌肉性、先天性和特发性脊柱侧弯）中，这种进展涉及冠状面中椎骨和椎间盘的楔形畸形增加，以及其他平面上较小程度的畸形。虽然机械调节的软骨内生长在很大程度上是造成渐进性椎体楔入的原因，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，因为伴随青少年椎体生长的椎间盘生长极少。拟议的研究将确定椎间盘如何应对骨骼不成熟的脊柱侧凸脊柱中发生的压力变化。骨骼未成熟的大鼠尾部模型已表现出脊柱侧凸中所见的椎骨楔入，将被扩展以确定椎间盘在成角畸形和压缩载荷下的变化。将比较长达 5 周的持续压缩和持续成角的三种排列。将测量加载和/或变形的以及相邻的对照盘，以确定形态、结构和机械变化、环组织成分（包括凸侧和凹侧）、蛋白质合成和细胞构成。将评估蛋白质合成以及参与椎间盘组织合成和降解的主要蛋白质的基因表达。研究结果将参考总体假设进行解释，即脊柱侧弯进展的椎间盘成分是由机械介导的凹侧椎间盘重塑和退变造成的，凹侧椎间盘长期承受较重的负荷。临床设计预防脊柱侧弯进展的早期干预措施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）。拟议的工作提高了对畸形进展的理解，从而允许设计新的治疗方法来恢复脊柱的对称生长。这些方法可能包括支架设计的改进、肌肉康复的新可能性以及旨在早期微创改变脊柱生长的外科手术。