Lotz J C, Colliou O K, Chin J R, Duncan N A, Liebenberg E
Department of Orthopaedic Surgery, University of California, San Francisco, California, USA.
Spine (Phila Pa 1976). 1998 Dec 1;23(23):2493-506. doi: 10.1097/00007632-199812010-00004.
An in vivo study of the biologic and biomechanical consequences of static compressive loading on the mouse tail intervertebral disc.
To determine whether static compression in vivo alters the biologic activity of the disc and leads to diminished biomechanical performance.
Static compressive stress that exceeds the disc's swelling pressure is known to change hydration and the intradiscal stress distribution. Alterations in hydration and stress have been associated with changes in disc cell activity in vitro and in other collagenous tissues in vivo.
Mouse tail discs were loaded in vivo with an external compression device. After 1 week at one of three different stress levels, the discs were analyzed for their biomechanical performance, morphology, cell activity, and cell viability. A second group of mice were allowed to recuperate for 1 month after the 1-week loading protocol to assess the disc's ability to recover. As an aid to interpreting the histologic and biologic data, finite-element analysis was used to predict region-specific changes in tissue stress caused by the static loading regimen.
With increasing compressive stress, the inner and middle anulus became progressively more disorganized, and the percentage of cells undergoing apoptosis increased. The expression of Type II collagen was suppressed at all levels of stress, whereas the expression of aggrecan decreased at the highest stress levels in apparent proportion to the decreased nuclear cellularity. Compression for 1 week did not affect the disc bending stiffness or strength but did increase the neutral zone by 33%. As suggested by the finite-element model, during sustained compression, tension is maintained in the outer anulus and lost in the inner and middle regions where the hydrostatic stress was predicted to increased nearly 10-fold. Discs loaded at the lowest stress recovered anular architecture but not cellularity after 1 month of recuperation. Discs loaded at the highest stress did not recover anular architecture, displaying islands of cartilage cells in the middle anulus at sites previously populated by fibroblasts.
The results of the current project demonstrate that static compressive loading initiates a number of harmful responses in a dose-dependent way: disorganization of the anulus fibrosus; an increase in apoptosis and associated loss of cellularity; and down regulation of collagen II and aggrecan gene expression. The finite element model used in this study predicts loss of collagen fiber tension and increased matrix hydrostatic stress in those anular regions observed to undergo programmed cell death after 1 week of loading and ultimately become populated by chondrocytes after one month of recuperation. This correspondence conforms with the suggestions of others that the cellular phenotype in collagenous tissues is sensitive to the dominant type of tissue stress. Although the specific mechanisms by which alterations in tissue stress lead to apoptosis and variation in cell phenotype remain to be identified, our results suggest that maintenance of appropriate stress within the disc may be an important basis for strategies to mitigate disc degeneration and initiate disc repair.
一项关于静态压缩负荷对小鼠尾部椎间盘生物及生物力学影响的体内研究。
确定体内静态压缩是否会改变椎间盘的生物活性并导致生物力学性能下降。
已知超过椎间盘肿胀压力的静态压缩应力会改变水合作用及椎间盘内应力分布。水合作用和应力的改变与体外椎间盘细胞活性变化以及体内其他胶原组织的变化有关。
使用外部压缩装置对小鼠尾部椎间盘进行体内加载。在三种不同应力水平之一加载1周后，分析椎间盘的生物力学性能、形态、细胞活性和细胞活力。第二组小鼠在1周加载方案后恢复1个月，以评估椎间盘的恢复能力。为辅助解释组织学和生物学数据，采用有限元分析来预测静态加载方案引起的组织应力区域特异性变化。
随着压缩应力增加，纤维环内层和中层逐渐变得更加紊乱，凋亡细胞百分比增加。在所有应力水平下，II型胶原蛋白的表达均受到抑制，而在最高应力水平下，聚集蛋白聚糖的表达下降，与细胞核细胞数量减少明显成比例。压缩1周未影响椎间盘的弯曲刚度或强度，但使中性区增加了33%。如有限元模型所示，在持续压缩过程中，纤维环外层保持张力，而内层和中层区域失去张力，预计此处静水压力增加近10倍。在最低应力水平加载的椎间盘在恢复1个月后恢复了纤维环结构，但细胞数量未恢复。在最高应力水平加载的椎间盘未恢复纤维环结构，在纤维环中层以前有成纤维细胞的部位出现软骨细胞岛。
本项目结果表明，静态压缩负荷以剂量依赖方式引发多种有害反应：纤维环紊乱；凋亡增加及相关细胞数量减少；II型胶原和聚集蛋白聚糖基因表达下调。本研究中使用的有限元模型预测，在加载1周后观察到经历程序性细胞死亡并最终在恢复1个月后被软骨细胞占据的那些纤维环区域，胶原纤维张力丧失且基质静水压力增加。这种对应关系符合其他人的观点，即胶原组织中的细胞表型对主要的组织应力类型敏感。尽管组织应力改变导致凋亡和细胞表型变化的具体机制仍有待确定，但我们的结果表明，维持椎间盘内适当的应力可能是减轻椎间盘退变和启动椎间盘修复策略的重要基础。
