BIOCHEMISTRY OF INTERVERTEBRAL DISC

大多数专家相信，退变的腰椎间盘在 这是许多腰背痛病例的根源。腰间盘只有 刚刚开始在分子水平上进行详细的研究，仍然是一个 特征不佳的结缔组织。我们建议在更多的 人和动物的间盘胶原的细节使用 最新的生化技术。重点将是试图将 结构才能发挥作用。一个重要的目标是理解 人类椎间盘特性随年龄增长的特征变化。这项工作 人类腰椎间盘最初将集中在腰椎间盘的尸检标本上 根据组织病理学检查精心挑选 对他们的年龄来说通常是正常的，没有肉眼损伤。兔子和牛 腰椎间盘也将被研究。胶原蛋白的分子种类将是 定量定位于纤维环和髓核内， 包括已知存在的大量I型和II型胶原蛋白 以及AlphaA、Alphab、1Alpha、2Alpha和3Alpha物种，它们可能是 现在时。这些胶原蛋白分布的部位相关变化 物种将与分布和分布的变化相关 蛋白多糖和非胶原蛋白的可萃取性，以及 组织的肿胀特性。胶原蛋白的交联残留物将 被分离和定量，包括羟基吡啶残留物， 成熟的形式。胃酶溶解的胶原蛋白将被分离成 个别物种、第I类、第II类等，以及 每个遗传物种的交链和其他化学性质都会 量过了。使用高效液相色谱(HPLC) 分离的胶原肽，分布的任何变化 羟基吡啶的交联度与年龄和在盘中的位置有关 评估过了。胶原环和核的分子堆积将是 经低角X射线衍射和电子显微镜观察， 例如，与年龄相关的水合变化。手术中取出的间盘 矫正脊柱侧弯和其他情况，包括脊椎滑脱 手，并将继续提供，也将进行研究。一个 将与贝斯的生物力学实验室展开合作 以色列医院将圆盘试件的粘弹性剪切模数联系起来 以及它们的组成。总而言之，目标是一个更好的 认识分子结构与年龄的关系 退化和机械故障。

Most experts are convinced that degenerating intervertebral discs are at the root of many cases of low-back pain. The intervertebral disc has only just begun to be studied in detail at the molecular level and is still a poorly characterized connective tissue. We propose to characterize in more detail the collagen of human and animal intervertebral discs using the latest biochemical techniques. The emphasis will be an attempt to relate structure to function. An important aim is to understand the characteristic changes in human disc properties with age. The work on human discs will focus initially on autopsy specimens of lumbar discs carefully selected on the basis of histopathological examination to be typically normal for their age, with no gross lesions. Rabbit and cow lumbar discs will also be studied. Molecular species of collagen will be mapped quantitatively within the annulus fibrosus and nucleus pulposus, including the bulk types I and II collagens that are known to be present and the AlphaA, AlphaB, 1Alpha, 2Alpha, and 3Alpha species which may be present. Site-related changes in the distribution of these collagen species will be correlated with variations in the distribution and extractability of proteoglycans and non-collagenous proteins, and with swelling properties of the tissue. Crosslinking residues of collagen will be isolated and quantified, including hydroxypyridinium residues, the mature forms. Pepsin-solubilized collagen will be fractionated into individual species, type I, type II, etc., and the level and type of crosslink in each genetic species and other chemical properties will be measured. Using high performance liquid chromatography (HPLC) to fractionate collagen peptides, any alterations in the distribution of hydroxypyridinium crosslinks with age and location in the disc will be assessed. The molecular packing of annulus and nucleus collagen will be examined by low angle X-ray diffraction and electron microscopy seeking, for example, age-related changes in hydration. Discs removed at surgery to correct scoliosis and other conditions, including spondylolisthesis are on hand and will continue to be available and will also be studied. A collaboration will be initiated with the biomechanics laboratory at Beth Israel Hospital to relate the visco-elastic shear modulus of disc specimens with their composition. In summary, the objective is a better understanding of the relationship between molecular structure, age-related degeneration and mechanical failure.