Senescence in cells of the aging and degenerating intervertebral disc -: Immunolocalization of senescence-associated β-galactosidase in human and sand rat discs
Senescence in cells of the aging and degenerating intervertebral disc -: Immunolocalization of senescence-associated β-galactosidase in human and sand rat discs
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DOI：
10.1097/01.brs.0000253960.57051.de
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发表时间：
2007-02-01
期刊：
影响因子：
3
通讯作者：
Hanley, Edward N., Jr.
中科院分区：
文献类型：
--
作者：
Gruber, Helen E.;Ingram, Jane A.;Hanley, Edward N., Jr.
研究设计.在细胞衰老的前瞻性研究中获得人椎间盘环组织。衰老生物标志物β-半乳糖苷酶（衰老相关β-半乳糖苷酶，SA-β-gal）的定位用于定量测定%衰老细胞。从手术标本或对照供体获得盘。还对沙鼠腰椎的椎间盘进行了研究。实验研究得到了作者的人类受试者机构审查委员会和动物使用委员会的批准。使用免疫细胞化学定量衰老生物标志物SA-β-gal阳性细胞的百分比，以确定Thompson I级至V级人类椎间盘中细胞衰老的发生率。背景数据总结。细胞衰老已被认为是一个潜在的因素发挥作用的年龄相关的椎间盘退变。衰老细胞是有活力的，但已经失去了分裂的能力。然而，衰老细胞是代谢活跃的。采用免疫细胞化学法对54例受试者的57个椎间盘标本进行抗SA-β-gal免疫细胞化学定位，以识别衰老细胞。用定量组织形态学方法测定阳性细胞比例。人椎间盘的定量组织形态测定显示SA-β-gal阳性细胞的总发生率为29.9%（+/- 24.8，SD），范围为0 - 92.01%。通过按Thompson分级分组的衰老细胞%的ANOVA分析显示，随着椎间盘退变的增加，衰老显著增加（P < 0.0001）。Tukey检验进一步分析显示I/II级与IV级和V级中的衰老细胞%之间存在显著差异。SA-β-gal阳性细胞也存在于衰老大鼠脊柱的椎间盘中。SA-β-gal免疫组织化学定位的定量分析确定了老化/退化椎间盘中的相当大的衰老细胞群体。重要的是要发现更多关于衰老的椎间盘细胞群，因为这些细胞随着时间的推移在椎间盘内持续存在和积累。由于衰老细胞不能分裂，衰老可能会降低椎间盘产生新细胞以取代因坏死或凋亡而失去的现有细胞的能力。
Study Design. Human intervertebral disc anulus tissue was obtained in a prospective study of cell senescence. Localization of the senescence biomarker beta-galactosidase ( senescence associated beta-galactosidase, SA-beta-gal) was used for quantitative determination of the % senescent cells. Discs were obtained from surgical specimens or control donors. Discs were also studied from the lumbar spine of the sand rat. Experimental studies were approved by the authors' Human Subjects Institutional Review Board and animal use committee.Objectives. To determine the incidence of cell senescence in human discs with Thompson Grades I through V using immunocytochemistry to quantify the percentage of cells positive for the senescence biomarker SA-beta-gal.Summary of Background Data. Cell senescence has been recognized as a potential factor playing a role age-related disc degeneration. Senescent cells are viable but have lost the ability to divide. Senescence cells, however, are metabolically active.Methods. Fifty-seven discs specimens from 54 subjects were examined with immunocytochemistry for anti-SA-beta-gal immunocytochemical localization to identify senescent cells. The fraction of positive cells was determined with quantitative histomorphometry.Results. Quantitative histomorphometry of human discs show an overall incidence of SA-beta-gal-positive cells of 29.9% ( +/- 24.8, SD), with a range from 0 to 92.01%. Analysis by ANOVA of the % senescent cells grouped by Thompson grade showed significant increases in senescence with increasing disc degeneration ( P < 0.0001). Further analysis with Tukey's test showed significant differences between the % senescent cells in Grades I/II versus IV, and versus V. SA-beta-gal-positive cells were also present in discs of the aging sand rat spine.Conclusions. Quantitative analysis of immunohistochemical localization of SA-beta-gal identified a sizeable population of senescent cells in the aging/degenerating disc. It is important to discover more about the senescent disc cell population because these cells persist and accumulate over time within the disc. Since senescent cells cannot divide, senescence may reduce the disc's ability to generate new cells to replace existing ones lost to necrosis or apoptosis.