Zheng Yi, Mei Liangwei, Li Shengyou, Ma Teng, Xia Bing, Hao Yiming, Gao Xue, Wei Bin, Wei Yitao, Jing Da, Luo Zhuojing, Huang Jinghui
Department of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Faculty of Life Sciences, Northwest University, Xi'an, China.
Front Bioeng Biotechnol. 2022 Mar 21;10:853872. doi: 10.3389/fbioe.2022.853872. eCollection 2022.
Intervertebral disc (IVD) degeneration is regarded as a major contributor to low back pain (LBP), causing serious economic burden on individuals and society. Unfortunately, there are limited effective treatment for IVD degeneration. Pulsed electromagnetic field (PEMF) is an economical and effective physical therapy method, with reduced side-effects. It offers certain protection to a number of degenerative diseases. Therefore, understanding the underlying mechanism of PEMF on IVD is important for improving the PEMF therapeutic efficiency. In this study, PEMF up-regulated extracellular matrix (ECM) related genes in degenerated nucleus pulposus (NP) cells. It also increased SIRT1 expression and promoted autophagy in degenerated NP cells. In contrast, the autophagy suppressor 3-methyladenine (3-MA) reversed the beneficial effect of PEMF on ECM production. Similarly, the SIRT1 enzyme activity suppressor EX 527 also inhibited the effect of PEMF on autophagy and ECM production in NP cells, thereby suggesting that PEMF regulated ECM related genes expression through SIRT1-autophagy signaling pathway. Lastly, PEMF significantly reduced IVD degeneration in a rat model of IVD degeneration . In summary, our study uncovers a critical role of SIRT1-dependent autophagy signaling pathway in ECM protection and thus in the establishment of therapeutic effect of PEMF on IVD degeneration.
椎间盘(IVD)退变被认为是导致腰痛(LBP)的主要原因,给个人和社会造成了沉重的经济负担。不幸的是,针对IVD退变的有效治疗方法有限。脉冲电磁场(PEMF)是一种经济有效的物理治疗方法,副作用较小。它对多种退行性疾病具有一定的保护作用。因此,了解PEMF对IVD的潜在作用机制对于提高PEMF的治疗效果至关重要。在本研究中,PEMF上调了退变髓核(NP)细胞中细胞外基质(ECM)相关基因的表达。它还增加了SIRT1的表达并促进了退变NP细胞中的自噬。相反,自噬抑制剂3-甲基腺嘌呤(3-MA)逆转了PEMF对ECM产生的有益作用。同样,SIRT1酶活性抑制剂EX 527也抑制了PEMF对NP细胞自噬和ECM产生的影响,从而表明PEMF通过SIRT1-自噬信号通路调节ECM相关基因的表达。最后,PEMF显著减轻了IVD退变大鼠模型中的IVD退变。总之,我们的研究揭示了SIRT1依赖性自噬信号通路在ECM保护中的关键作用,从而在PEMF对IVD退变的治疗效果确立中发挥关键作用。