Analysis of aging and degeneration of the human intervertebral disc - Comparison of surgical specimens with normal controls
Analysis of aging and degeneration of the human intervertebral disc - Comparison of surgical specimens with normal controls
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DOI：
10.1097/00007632-199804010-00001
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发表时间：
1998-04-01
期刊：
影响因子：
3
通讯作者：
Hanley, EN
中科院分区：
文献类型：
--
作者：
Gruber, HE;Hanley, EN
研究设计.对33例对照组和39例手术组腰椎间盘标本进行前瞻性分析，以评估椎间盘细胞外基质的产生和细胞功能。本研究的作者分析了I、II、III和VI型胶原的免疫组织化学分布、凋亡椎间盘细胞的原位定位和抗酒石酸酸性磷酸酶的定位。定量细胞凋亡的发生率。纤维环细胞死亡;检查胶原蛋白在细胞周围、区域和区域间基质中的分布;检查基质细胞变性;并将患病组织与对照个体的正常组织进行比较。以前的研究椎间盘组织病理学集中在细胞外基质形态和生化合成和：退行性变化，但很少了解有关的细胞;人口内的光盘负责;这些变化。在这项研究中，光学显微镜，免疫组织化学，酶组织化学，原位杂交被用来检查33例患者和39例对照标本的人类纤维环获得通过手术程序或捐赠者合作的人：组织网络。对照组中凋亡细胞死亡的高发生率明显更高（73.1 +/- 5.1% [平均值+/- SEM]; n = 20）（53.5 ± 5.6%; n = 20; P < 0.001）;这可能是由于对照人群的平均年龄明显更大（57.2 +/- 3.1年）与患者人群（44.3 +/- 3.2年; P < 0.001）相比。免疫组化结果显示，在两个研究组中，在衰老和退变过程中，椎间盘细胞周围的细胞外结构域发生了很大的变化。酶：组织化学显示在人类椎间盘细胞中存在抗酒石酸酸性磷酸酶活性。这些发现揭示了椎间盘中细胞凋亡的发生率很高。存活的细胞不是合成不活跃的，而是在衰老和退化期间产生不适当的基质产物。在某些情况下，似乎细胞周围的基质可能形成隔离屏障，这可能影响单个细胞的活性和细胞间通讯。这些结果表明，需要1）更全面地了解通过细胞凋亡导致椎间盘细胞死亡的原因，并确定这种程序性细胞死亡是否可以保留或停止，以及2）更全面地了解椎间盘细胞与周围细胞外基质之间的动态关系，它们产生并重塑。调节椎间盘细胞外基质-椎间盘细胞稳态的因素尚不清楚，细胞外基质和椎间盘细胞功能调节之间的关系也是未知的。本研究的形态学结果表明，这些问题是椎间盘细胞生物学的重要考虑因素。在椎间盘细胞中抗酒石酸酸性磷酸酶活性的鉴定为椎间盘细胞外基质重塑的研究提供了一个新的领域。总之，这些新的观点提供了评估椎间盘细胞健康和功能的新参数。
Study Design. A prospective analysis of 33 control and 39 surgical human lumbar disc specimens from the anulus was undertaken to assess disc cell extracellular matrix production and cell function. The authors of this study analyzed immunohistochemical distributions of Types I, II, III and VI collagen, in situ localization of apoptotic disc cells, and tartrate-resistant acid phosphatase localization.Objectives. To quantify the incidence of apoptotic. cell death in the anulus; examine the collagen distribution in the pericellular, territorial, and interterritorial matrix; examine matrix cell degeneration; and compare diseased tissue with normal tissue from control individuals.Summary of the Background Data. Previous studies of disc histopathology have focused on extracellular matrix morphology and on biochemical synthetic and : degenerative changes, but little is understood about the cell;populations within the disc that are responsible for ;these changes.Methods. In this study light microscopy, immunohistochemistry, enzyme histochemistry, and in situ hybridization were used to examine 33 patient and 39 control specimens of human anulus obtained either via surgical procedures or from donors to the Cooperative Human :Tissue Network.Results. The high incidence of apoptotic cell death was significantly greater in the control group (73.1 +/- 5.1% [mean +/- SEM]; n = 20) than among surgical specimens (53.5 +/- 5.6%; n = 20; P < 0.001); this was probably a a result of the significantly greater average age in the control population (57.2 +/- 3.1 years) compared with that in the patient population (44.3 +/- 3.2 years; P < 0.001). Immunohistochemistry yielded findings that led to an expanded appreciation of the greatly modified extracellular domains that surrounded disc cells during aging and degeneration in both study groups. Enzyme : histochemistry revealed the presence of tartrate-resistant acid phosphatase activity in human disc cells.Conclusions. These findings reveal that there is a high incidence of apoptosis in the intervertebral disc. Surviving cells are not synthetically inactive but are, rather, producing inappropriate matrix products during aging and degeneration. In certain instances it appears that the matrix surrounding the cell may form an isolation barrier, which may influence individual cell activity and intercellular communication. These results point to the need to 1) more fully understand the cause of disc cell death via apoptosis and to determine whether this programmed cell death can be reserved or halted, and 2) more fully understand the dynamic relation between disc cells and the surrounding extracellular matrix, which they produce and remodel. The factors regulating extracellular matrix-disc cell homeostasis in the disc are unknown, as is the relation between extracellular matrix and disc cell functional modulation. The morphologic findings of this study suggest that these issues are important considerations in disc cell biology. The identification of tartrate-resistant acid phosphatase activity in disc cells allows for a new area of study of disc extracellular matrix remodelling. In summary, these new perspectives provide new parameters with which to assess disc cell health and function.