Li Hui, Kelley Joshua, Ye Yiqing, Ye Zhi-Wei, Townsend Danyelle M, Zhang Jie, Wu Yongren
Department of Bioengineering, Clemson University, Charleston, SC 29425, USA.
Department of Orthopaedics and Physical Medicine & Rehabilitation, Medical University of South Carolina, Charleston, SC 29425, USA.
Cells. 2025 Apr 19;14(8):613. doi: 10.3390/cells14080613.
Low back pain is a widespread condition that significantly impacts quality of life, with intervertebral disc degeneration (IDD) being a major contributing factor. However, the underlying mechanisms of IDD remain poorly understood, necessitating further investigation. Environmental risk factors, such as mechanical stress and cigarette smoke, elevate reactive oxygen species levels from both endogenous and exogenous sources, leading to redox imbalance and oxidative stress. The endoplasmic reticulum (ER) and mitochondria, two key organelles responsible for protein folding and energy production, respectively, are particularly vulnerable to oxidative stress. Under oxidative stress conditions, ER stress and mitochondrial dysfunction occur, resulting in unfolded protein response activation, impaired biosynthetic processes, and disruptions in the tricarboxylic acid cycle and electron transport chain, ultimately compromising energy metabolism. Prolonged and excessive ER stress can further trigger apoptosis through ER-mitochondrial crosstalk. Given the unique microenvironment of the intervertebral disc (IVD)-characterized by hypoxia, glucose starvation, and region-specific cellular heterogeneity-the differential effects of environmental stressors on distinct IVD cell populations require further investigation. This review explores the potential mechanisms through which environmental risk factors alter IVD cell activities, contributing to IDD progression, and discusses future therapeutic strategies aimed at mitigating disc degeneration.
腰痛是一种普遍存在的病症，严重影响生活质量，其中椎间盘退变（IDD）是一个主要促成因素。然而，IDD的潜在机制仍知之甚少，需要进一步研究。环境风险因素，如机械应力和香烟烟雾，会升高内源性和外源性的活性氧水平，导致氧化还原失衡和氧化应激。内质网（ER）和线粒体，分别是负责蛋白质折叠和能量产生的两个关键细胞器，特别容易受到氧化应激的影响。在氧化应激条件下，会发生内质网应激和线粒体功能障碍，导致未折叠蛋白反应激活、生物合成过程受损以及三羧酸循环和电子传递链中断，最终损害能量代谢。长期和过度的内质网应激可通过内质网-线粒体相互作用进一步触发细胞凋亡。鉴于椎间盘（IVD）独特的微环境——其特点是缺氧、葡萄糖饥饿和区域特异性细胞异质性——环境应激源对不同IVD细胞群的不同影响需要进一步研究。本综述探讨了环境风险因素改变IVD细胞活动、导致IDD进展的潜在机制，并讨论了旨在减轻椎间盘退变的未来治疗策略。
