Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways
Apoptosis of human intervertebral discs after trauma compares to degenerated discs involving both receptor-mediated and mitochondrial-dependent pathways
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DOI：
10.1002/jor.20601
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发表时间：
2008-07-01
影响因子：
2.8
通讯作者：
Heyde, Christoph-E.
中科院分区：
文献类型：
--
作者：
Tschoeke, Sven K.;Hellmuth, Markus;Heyde, Christoph-E.
胸腰椎骨折的手术和非手术治疗方案中，创伤后椎间盘退变伴连续复位丢失和后凸畸形仍然是一个有争议的问题。椎间盘细胞凋亡在椎间盘退变过程中起重要作用。为了评价和比较骨化调节信号机制，从胸腰椎骨折患者（n = 21）、患有症状性IVD退变的患者（n = 6）和接受手术切除原发性椎体肿瘤的患者（n = 3用作对照样本）中获得IVD。前瞻性分析了所有组织的半胱天冬酶-3/7、-8和-9活性、凋亡受体表达水平以及与caspase结合的凋亡调节蛋白Bax和Bcl-2的基因表达。通过H&E染色证实凋亡细胞死亡的形态学变化特征。使用Student t检验将统计学显著性指定为p < 0.05。创伤性和退行性IVD均表现出caspase-3/7活性显著增加，并伴有明显的细胞凋亡。虽然胱天蛋白酶-3/7的活化显着更大的退化光盘，都显示出同样显着的激活的启动子胱天蛋白酶8和9。创伤性IVD单独表现出Fas受体（FasR）的显著增加，而TNF受体I（TNFR I）在两个病态IVD组中同样上调。只有创伤IVD表现出明显的变化，上调TNF的表达，除了显着下调抗凋亡Bcl-2蛋白。我们的研究结果表明，创伤后椎间盘的变化可能会促进和放大的内在的神经元介导的和外在的受体介导的细胞凋亡信号通路，这可能是，部分，一个可能的解释发展随后的椎间盘退变。(C)2008骨科研究学会。由威利期刊公司出版
Post-traumatic disc degeneration with consecutive loss of reduction and kyphosis remains a debatable issue within both the operative and nonoperative treatment regimen of thoracolumbar spine fractures. Intervertebral disc (IVD) cell apoptosis has been suggested to play a vital role in promoting the degeneration process. To evaluate and compare apoptosis-regulating signaling mechanisms, IVDs were obtained from patients with thoracolumbar spine fractures (n = 21), patients suffering from symptomatic IVD degeneration (n = 6), and from patients undergoing surgical resection of a primary vertebral tumor (n = 3 used as control samples). All tissues were prospectively analyzed in regards to caspase-3/7, -8, and -9 activity, apoptosis-receptor expression levels, and gene expression of the mitochondria-bound apoptosis-regulating proteins Bax and Bcl-2. Morphologic changes characteristic for apoptotic cell death were confirmed by H&E staining. Statistical significance was designated at p < 0.05 using the Student's t-test. Both traumatic and degenerative IVD demonstrated a significant increase of caspase-3/7 activity with evident apoptosis. Although caspase-3/7 activation was significantly greater in degenerated discs, both showed equally significant activation of the initiator caspases 8 and 9. Traumatic IVD alone demonstrated a significant increase of the Fas receptor (FasR), whereas the TNF receptor I (TNFR I) was equally up-regulated in both morbid IVD groups. Only traumatic IVD showed distinct changes in up-regulated TNF expression, in addition to significantly down-regulated antiapoptotic Bcl-2 protein. Our results suggest that post-traumatic disc changes may be promoted and amplified by both the intrinsic mitochondria-mediated and extrinsic receptor-mediated apoptosis signaling pathways, which could be, in part, one possible explanation for developing subsequent disc degeneration. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.