过度载荷通过诱导椎间盘细胞凋亡在椎间盘退变过程中发挥了重要作用，但椎间盘细胞凋亡的力学生物信号转导机制目前并不清楚。本项目首先通过动物模型观察整合素、G蛋白、受体酪氨酸激酶和牵张激活性离子通道等分子结构是否与动静力失衡所致的大鼠腰椎间盘退变以及椎间盘细胞凋亡相关；其次通过体外细胞培养检测整合素、G蛋白、受体酪氨酸激酶和牵张激活性离子通道在过度载荷诱导的椎间盘细胞凋亡过程中的相对重要性及其各自的下游信号分子；最后通过体内、外实验观察整合素RNA干扰对过度载荷诱导的椎间盘细胞凋亡以及动物模型椎间盘退变的影响。通过本项目试图阐明应力诱导椎间盘细胞凋亡的力学生物信号转导机制，并为椎间盘退变的生物学防治开辟新思路与新途径。

Over-loading plays an important role in intervertebral disc degeneration by inducing disc cell apoptosis, the mechano-biology signal transduction in this process, however, needs further investigation. The current project attempts to elucidate the mechanism how mechanical stimuli transfer to biological response in over-loading induced disc cell apoptosis. Firstly, the expression of integrins, G-proteins, receptor tyrosine kinases, and stretch-activated ion channels, will be detected by molecular biological methods in degenerated disc tissues from rat models of intervertebral disc degeneration induced by unbalanced dynamic and static forces of the lumbar spine. Secondly, by using a novel culture system, the relative importance of integrins, G-proteins, receptor tyrosine kinases and stretch-activated ion channels, as well as their downstream elements in over-loading induced disc cell apoptosis, will be observed in vitro. Finally, the role of integrin RNA interference in suppressing disc cell apoptosis and in retarding the development of intervertebral disc degeneration will also be investigated. The results of this project will help to better understand the pathogenesis of intervertebral disc degeneration and may provide potential therapy for it.