Fan Chunyang, Chu Genglei, Yu Zilin, Ji Zhongwei, Kong Fanchen, Yao Lingye, Wang Jiale, Geng Dechun, Wu Xiexing, Mao Haiqing
Department of Orthopaedic Surgery, Orthopaedic Institute, The First Affiliated Hospital, Suzhou Medical College, Soochow University, Suzhou, Jiangsu, China.
Department of Pain Management, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.
Front Cell Dev Biol. 2023 Jul 27;11:1219840. doi: 10.3389/fcell.2023.1219840. eCollection 2023.
Nucleus pulposus, annulus fibrosus, and cartilage endplate constitute an avascular intervertebral disc (IVD), which is crucial for spinal and intervertebral joint mobility. As one of the most widespread health issues worldwide, intervertebral disc degeneration (IVDD) is recognized as a key contributor to back and neck discomfort. A number of degenerative disorders have a strong correlation with ferroptosis, a recently identified novel regulated cell death (RCD) characterized by an iron-dependent mechanism and a buildup of lipid reactive oxygen species (ROS). There is growing interest in the part ferroptosis plays in IVDD pathophysiology. Inhibiting ferroptosis has been shown to control IVDD development. Several studies have demonstrated that in TBHP-induced oxidative stress models, changes in ferroptosis marker protein levels and increased lipid peroxidation lead to the degeneration of intervertebral disc cells, which subsequently aggravates IVDD. Similarly, IVDD is significantly relieved with the use of ferroptosis inhibitors. The purpose of this review was threefold: 1) to discuss the occurrence of ferroptosis in IVDD; 2) to understand the mechanism of ferroptosis and its role in IVDD pathophysiology; and 3) to investigate the feasibility and prospect of ferroptosis in IVDD treatment.
髓核、纤维环和软骨终板构成了一个无血管的椎间盘（IVD），它对脊柱和椎间关节的活动至关重要。作为全球最普遍的健康问题之一，椎间盘退变（IVDD）被认为是导致背部和颈部不适的关键因素。许多退行性疾病与铁死亡密切相关，铁死亡是一种最近发现的新型程序性细胞死亡（RCD），其特征是依赖铁的机制和脂质活性氧（ROS）的积累。铁死亡在IVDD病理生理学中所起的作用越来越受到关注。已证明抑制铁死亡可控制IVDD的发展。多项研究表明，在叔丁基过氧化氢（TBHP）诱导的氧化应激模型中，铁死亡标记蛋白水平的变化和脂质过氧化增加会导致椎间盘细胞退变，进而加重IVDD。同样，使用铁死亡抑制剂可显著缓解IVDD。本综述的目的有三个：1）讨论IVDD中铁死亡的发生；2）了解铁死亡的机制及其在IVDD病理生理学中的作用；3）研究铁死亡在IVDD治疗中的可行性和前景。
