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RECOVERY OF INTERVERTEBRAL DISC AFTER ENZYME TREATMENT

酶治疗后椎间盘的恢复

基本信息

批准号：
2078815
负责人：
Theodore Richard Oegema
金额：
$ 22.28万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-04-01 至 1998-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2078815
关键词：
aging autoradiography biomarker collagen disease /disorder model dogs enzyme therapy extracellular matrix gene expression human tissue immunofluorescence technique in situ hybridization intervertebral disk surgery link protein phenotype proteoglycan spinal disk injury tissue /cell culture

项目摘要

DESCRIPTION: (Adapted From Investigator's Abstract) Disc degeneration which causes significant disability and loss of the quality of life, involves cellular, nutritional and mechanical components. The investigators hypothesize that cellular changes occur early and will test two hypotheses. The first is that there is a loss of normal matrix producing phenotype of cells in the nucleus pulposus and an increase of a fibrotic phenotype. This may be reversible as a result of changes in environment or irreversible. This phenotype may also be more sensitive to catabolic cytokines. The second hypothesis is that notochordal cells, which are critical to the development of nucleus pulposus, also play a role either directly by synthesis of matrix components or indirectly by influencing the other cells in the nucleus delaying early changes; and their loss accelerates degeneration.In order to test the first hypothesis, which considerable preliminary data supports, both matrix producing cells (MPC) and nonmatrix producing cells (NMPC) will be isolated from human disc and characterized from normal and degenerative discs. Sensitivity to IGF-1, TGF-B1, il-1B, and TNF-a will be examined.Co-culture experiments will be used to determine if interactions between the two cell populations occur. Because proteoglycans (PGs) represent a major extracellular matrix component, show changes that are highly correlated with aging and degeneration, and have turnover rapid enough to reflect short-term changes in the matrix, PGs and their associated link proteins will be used as indicator molecules. Presence of hyaluronic acid-binding regions, the cleavage of the protein core in chondroitin sulfate (CS) or keratan sulfate (KS) rich regions, and the presence and ratios of link proteins 1, 2, and 3 will be examined. Collagen types will also be determine. To test hypothesis two, notochordal cells will be isolated from nonchondrodystrophoid canine nucleus pulposus, a unique source of large amounts of these cells, and their characteristics determined with respect to matrix synthesis, turnover, and response to the growth factors and cytokines. Co-cultures with MPC and/or NMPC will determine if there are interactions between the different cell types. Key observations will be confirmed with human notochordal cells.

描述：(改编自《调查者摘要》)椎间盘退变这会导致严重的残疾和生活质量的损失，包括细胞、营养和机械组件。这个研究人员假设细胞变化发生得较早，并将测试两个假设。第一个是正规矩阵的损失髓核细胞的产生表型和增加一种纤维化表型。这可能是可逆的，因为环境还是不可逆转的。这种表型也可能更敏感。分解代谢的细胞因子。第二种假设是脊索神经对髓核发育至关重要的细胞也直接通过合成基质成分发挥作用，或者间接地通过影响细胞核中的其他细胞来延迟早期变化；并且它们的丢失加速退化。为了测试第一个假说，有相当多的初步数据支持，两者都基质产生细胞(MPC)和非基质产生细胞(NMPC)将从人类椎间盘中分离出来，其特征是与正常和退变的椎间盘。对胰岛素样生长因子-1、转化生长因子-β、白介素1β和肿瘤坏死因子-α的敏感性接受检查。将使用共同文化实验来确定这两个细胞群之间会发生相互作用。因为蛋白多糖(PG)代表一种主要的细胞外基质组件，显示与老化高度相关的更改退化，并有足够快的周转速度来反映短期基质、前列腺素及其相关连接蛋白的变化将是用作指示剂分子。存在透明质酸结合区域，硫酸软骨素(CS)蛋白核心的切割或角蛋白硫酸盐(KS)富集区，以及我们将研究连接蛋白1、2和3。胶原蛋白类型也会心意坚定。为了检验假设二，脊索细胞将是从非软骨营养不良犬髓核中分离出一种独特的大量这些细胞的来源及其特征根据矩阵合成、周转和响应确定生长因子和细胞因子。与MPC和/或NMPC共培养将确定不同细胞类型之间是否存在交互作用。关键的观察结果将在人类脊索细胞中得到证实。