Programmed NP Cell Death Induced by Mitochondrial ROS in a One-Strike Loading Disc Degeneration Organ Culture Model.
Programmed NP Cell Death Induced by Mitochondrial ROS in a One-Strike Loading Disc Degeneration Organ Culture Model.
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一次性加载椎间盘退变器官培养模型中线粒体 ROS 诱导的程序性 NP 细胞死亡
DOI：
10.1155/2021/5608133
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发表时间：
2021
影响因子：
--
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Li BL;Liu X;Gao M;Zhang F;Chen X;He Z;Wang J;Tian W;Chen D;Zhou Z;Liu S
越来越多的证据表明，线粒体活性氧（ROS）在机械应力诱导的腰椎间盘退行性疾病（DDD）中发挥着关键作用。然而，详细的病理机制需要进一步研究。在这项研究中，我们利用一次打击加载椎间盘退变器官培养模型，探讨椎间盘（IVD）对机械应力的反应。使IVD经受盘高度的40%的应变1秒，然后在生理负荷下培养。将甲磺酸米托醌（MitoQ）或其他抑制剂注射到IVD中。仅进行生理负荷培养的IVD用作对照。机械应力后即刻线粒体膜电位显著降低（P < 0.01）。ROS阳性细胞的百分比在机械应力后的前12小时显著增加，然后在48小时降至低水平。经MitoQ或鱼藤酮预处理后，ROS阳性细胞比例明显降低（P < 0.01）。髓核（NP）细胞活力在机械应力后12小时急剧下降，并在48小时达到稳定状态。虽然在机械应力后12小时，坏死性凋亡和凋亡相关标志物的水平显著增加，但在第7天未观察到显著变化。用MitoQ预处理增加了NP细胞活力，并在机械应力后12小时减轻了标志物变化。线粒体ROS水平升高也与细胞外基质（ECM）变性体征相关，包括分解代谢标志物上调、合成代谢标志物下调、糖胺聚糖（GAG）损失增加、IVD动态压缩刚度降低和机械应力后早期时间点的形态学降解变化。MitoQ预处理缓解了机械应力后12小时的一些退行性变化。这些变化在第7天消除。总之，我们的研究结果表明，线粒体活性氧作为重要的调节程序NP细胞死亡和ECM变性在体外受精后早期时间点机械应力。
Increasing evidence has indicated that mitochondrial reactive oxygen species (ROS) play critical roles in mechanical stress-induced lumbar degenerative disc disease (DDD). However, the detailed underlying pathological mechanism needs further investigation. In this study, we utilized a one-strike loading disc degeneration organ culture model to explore the responses of intervertebral discs (IVDs) to mechanical stress. IVDs were subjected to a strain of 40% of the disc height for one second and then cultured under physiological loading. Mitoquinone mesylate (MitoQ) or other inhibitors were injected into the IVDs. IVDs subjected to only physiological loading culture were used as controls. Mitochondrial membrane potential was significantly depressed immediately after mechanical stress (P < 0.01). The percentage of ROS-positive cells significantly increased in the first 12 hours after mechanical stress and then declined to a low level by 48 hours. Pretreatment with MitoQ or rotenone significantly decreased the proportion of ROS-positive cells (P < 0.01). Nucleus pulposus (NP) cell viability was sharply reduced at 12 hours after mechanical stress and reached a stable status by 48 hours. While the levels of necroptosis- and apoptosis-related markers were significantly increased at 12 hours after mechanical stress, no significant changes were observed at day 7. Pretreatment with MitoQ increased NP cell viability and alleviated the marker changes by 12 hours after mechanical stress. Elevated mitochondrial ROS levels were also related to extracellular matrix (ECM) degeneration signs, including catabolic marker upregulation, anabolic marker downregulation, increased glycosaminoglycan (GAG) loss, IVD dynamic compressive stiffness reduction, and morphological degradation changes at the early time points after mechanical stress. Pretreatment with MitoQ alleviated some of these degenerative changes by 12 hours after mechanical stress. These changes were eliminated by day 7. Taken together, our findings demonstrate that mitochondrial ROS act as important regulators of programmed NP cell death and ECM degeneration in IVDs at early time points after mechanical stress.
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影响因子：
7.2
作者：
Ding, Fan;Shao, Zeng-Wu;Xiong, Li-Ming
通讯作者：
Xiong, Li-Ming
影响因子：
2.4
作者：
Schultz DS;Rodriguez AG;Hansma PK;Lotz JC
通讯作者：
Lotz JC
影响因子：
--
作者：
Lin H;Peng Y;Li J;Wang Z;Chen S;Qing X;Pu F;Lei M;Shao Z
通讯作者：
Shao Z
影响因子：
5.7
作者：
Li, Zhen;Gehlen, Yannik;Lang, Gernot
通讯作者：
Lang, Gernot
影响因子：
3.1
作者：
Alkhatib, B.;Rosenzweig, D. H.;Haglund, L.
通讯作者：
Haglund, L.