Tschoeke Sven K, Hellmuth Markus, Hostmann Arwed, Robinson Yohan, Ertel Wolfgang, Oberholzer Andreas, Heyde Christoph-E
Department of Trauma and Reconstructive Surgery, Charité-University Hospitals Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin, Germany.
J Orthop Res. 2008 Jul;26(7):999-1006. doi: 10.1002/jor.20601.
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.
创伤后椎间盘退变伴连续的复位丧失和后凸畸形，在胸腰椎骨折的手术和非手术治疗方案中仍是一个有争议的问题。椎间盘（IVD）细胞凋亡被认为在促进退变过程中起重要作用。为了评估和比较凋亡调节信号机制，从胸腰椎骨折患者（n = 21）、有症状的IVD退变患者（n = 6）以及接受原发性椎体肿瘤手术切除的患者（n = 3用作对照样本）中获取IVD。对所有组织进行前瞻性分析，检测半胱天冬酶-3/7、-8和-9的活性、凋亡受体表达水平以及线粒体结合的凋亡调节蛋白Bax和Bcl-2的基因表达。通过苏木精-伊红染色确认凋亡细胞死亡的形态学变化。使用学生t检验，p < 0.05表示具有统计学意义。创伤性和退行性IVD均显示半胱天冬酶-3/7活性显著增加，伴有明显凋亡。虽然退变椎间盘中半胱天冬酶-3/7的激活明显更强，但两者均显示起始半胱天冬酶8和9的激活同样显著。仅创伤性IVD显示Fas受体（FasR）显著增加，而肿瘤坏死因子受体I（TNFR I）在两个病变IVD组中均同样上调。除了抗凋亡Bcl-2蛋白显著下调外，仅创伤性IVD显示肿瘤坏死因子表达上调有明显变化。我们的结果表明，创伤后椎间盘变化可能由内在的线粒体介导和外在的受体介导的凋亡信号通路促进和放大，这可能部分解释了随后发生的椎间盘退变。
