Caspase 3 Silencing Inhibits Biomechanical Overload-induced Intervertebral Disc Degeneration

Caspase 3 沉默抑制生物力学过载引起的椎间盘退变

• 批准号: 23592150
• 负责人: SUDO HIDEKI
• 金额: $ 3.33万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23592150/
• 关键词: アポトーシス; 椎間板; 変性制御; 椎間板組織; 生体力学

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.

椎间盘（IVD）退变在全球大部分人群中引起使人衰弱的腰痛。由于其发病机制尚不清楚，目前尚无有效的治疗方法。退变早期的一个特征性事件是嵌入IVD中的髓核（NP）细胞的凋亡。过度的生物力学负荷也可能是IVD退变的主要病因。本研究使用体外和体内压缩负荷模型来阐明IVD变性的潜在机制。此外，我们还研究了抑制细胞凋亡是否是一种潜在的临床治疗策略，用于治疗生物力学应力诱导的IVD退变。本研究表明，caspase 3 siRNA通过抑制NP细胞凋亡和基质降解酶的表达来减轻过载诱导的IVD退变。