Caspase 3 Silencing Inhibits Biomechanical Overload-induced Intervertebral Disc Degeneration

椎间盘退行性变在世界范围内的大部分人群中会导致衰弱的下腰痛。由于发病机制尚不清楚，目前尚无有效的治疗方法。退变早期的一个特征性事件是IVD中嵌入的髓核(NP)细胞的凋亡。生物力学负荷过大也可能是IVD退变的主要原因。本研究使用体外和体内压缩负荷模型来阐明IVD退变的潜在机制。此外，我们还探讨了抑制细胞凋亡是否是治疗生物力学应激诱导的IVD变性的一种潜在的临床治疗策略。本研究表明，caspase 3 siRNA通过抑制NP细胞的凋亡和基质降解酶的表达来减轻超负荷诱导的IVD变性。

Intervertebral disc (IVD) degeneration causes debilitating low back pain in large sections of the worldwide population. No efficient treatment currently exists because the unclear pathogenesis. One characteristic event early in the degeneration is the apoptosis of nucleus pulposus (NP) cells embedded in IVD. Excessive biomechanical loading may be also a major etiology of IVD degeneration. The present study used in vitro and in vivo models of compressive loading to elucidate the underlying mechanism of IVD degeneration. In addition, we investigated whether the inhibition of apoptosis is a potential clinical therapeutic strategy for the treatment of IVD degeneration induced by biomechanical stress.The present study suggests that caspase 3 siRNA attenuates overload-induced IVD degeneration by inhibiting NP cell apoptosis and the expression of matrix-degrading enzymes.