Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc
Role of death receptor, mitochondrial and endoplasmic reticulum pathways in different stages of degenerative human lumbar disc
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DOI：
10.1007/s10495-011-0644-7
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发表时间：
2011-10-01
期刊：
影响因子：
7.2
通讯作者：
Liu, Ting
中科院分区：
文献类型：
--
作者：
Wang, Hua;Liu, Hui;Liu, Ting
椎间盘细胞凋亡在椎间盘退变过程中起重要作用。研究表明，IVD细胞凋亡通过死亡受体、线粒体或内质网（ER）途径发生。我们的研究旨在探讨这三种途径与IVD变性（IVDD）程度的关系。IVD收集自腰椎骨折、椎体肿瘤、椎间盘突出或腰椎滑脱患者。通过MRI和组织形态学检查鉴别IVD，TUNEL染色检测细胞凋亡。采用RT-PCR和Western blot检测3条凋亡途径的生物标志物。并分析凋亡途径生物标志物与椎间盘病理的相关性。髓核细胞密度随退变进程而降低，凋亡率增加。IVDD轻、中度以ER途径为主（GRP 78、GADD 153表达上调和caspase-4激活），轻、中度以死亡受体途径为主（Fas、FasL表达上调和caspase-8激活），中、重度以线粒体途径为主（Bcl-2表达下调、Bax表达上调、细胞色素c在胞浆内积聚和caspase-9激活）。Fas、FasL、Bax、GADD 153、cytochrome-c和cleaved caspase-8/9/3的表达在包含型和非包含型椎间盘之间有显著性差异。总之，IVDD中细胞凋亡是通过这三种细胞凋亡途径共同发生的。ER途径在轻度IVDD中起着比中重度IVDD更重要的作用，死亡受体途径在轻度和中度IVDD中起着重要的作用，线粒体途径在中重度IVDD中起着重要的作用。椎间盘细胞凋亡可能在突出后迅速进展，并可能取决于突出的类型。
Intervertebral disc (IVD) cell apoptosis has been suggested to play an important role in promoting the degeneration process. It has been demonstrated that IVD cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic reticulum (ER) pathway. Our study aimed to explore the relationship among these three pathways and grade of IVD degeneration (IVDD). IVDs were collected from patients with lumbar fracture, vertebral tumor, disc herniation or spondylolisthesis. IVDs were distinguished by MRI and histomorphological examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore, the correlation between apoptosis pathways biomarkers and disc pathology were analyzed. Nucleus pulposus cell density decreased with degeneration process, and increased apoptotic ratio. ER pathway was predominant in mild stage of IVDD (GRP78, GADD153 upregulation and caspase-4 activation), death receptor pathway was predominant in mild and moderate stages (Fas, FasL up-regulation and caspase-8 activation) and mitochondrial pathway was predominant in moderate and severe stages (Bcl-2 down-regulation, Bax up-regulation, cytochrome-c accumulation in cytoplasm and caspase-9 activation). There were significant differences in the expressions of Fas, FasL, Bax, GADD153, cytochrome-c and cleaved caspase-8/9/3 between contained and non-contained discs. In conclusion, apoptosis occurs via these three apoptosis pathways together in IVDD. ER pathway plays a more critical role in the mild compared to moderate and severe stages, death receptor pathway in mild and moderate, and mitochondrial pathway in moderate and severe stages of IVDD. Disc cells apoptosis may progress rapidly after herniation, and may depend on the type of herniation.