Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies

IF 5.9 1区 医学 Q1 ORTHOPEDICS Journal of Orthopaedic Translation Pub Date : 2024-10-16 DOI:10.1016/j.jot.2024.08.016
Hao Zhou , Chenyu Wu , Yuxin Jin , Ouqiang Wu , Linjie Chen , Zhenyu Guo , Xinzhou Wang , Qizhu Chen , Kenny Yat Hong Kwan , Yan Michael Li , Dongdong Xia , Tao Chen , Aimin Wu
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Abstract

Background

Intervertebral disc degeneration (IVDD) is widely recognized as one of the leading causes of low back pain. Intervertebral disc cells are the main components of the intervertebral disc (IVD), and their functions include synthesizing and secreting collagen and proteoglycans to maintain the structural and functional stability of the IVD. In addition, IVD cells are involved in several physiological processes. They help maintain nutrient metabolism balance in the IVD. They also have antioxidant and anti-inflammatory effects. Because of these roles, IVD cells are crucial in IVDD. When IVD cells are subjected to oxidative stress, mitochondria may become damaged, affecting normal cell function and accelerating degenerative changes. Mitochondria are the energy source of the cell and regulate important intracellular processes. As a key site for redox reactions, excessive oxidative stress and reactive oxygen species can damage mitochondria, leading to inflammation, DNA damage, and apoptosis, thus accelerating disc degeneration.

Aim of review

Describes the core knowledge of IVDD and oxidative stress. Comprehensively examines the complex relationship and potential mechanistic pathways between oxidative stress, mitochondrial dysfunction and IVDD. Highlights potential therapeutic targets and frontier therapeutic concepts. Draws researchers' attention and discussion on the future research of all three.

Key scientific concepts of review

Origin, development and consequences of IVDD, molecular mechanisms of oxidative stress acting on mitochondria, mechanisms of oxidative stress damage to IVD cells, therapeutic potential of targeting mitochondria to alleviate oxidative stress in IVDD.

The translational potential of this article

Targeted therapeutic strategies for oxidative stress and mitochondrial dysfunction are particularly critical in the treatment of IVDD. Using antioxidants and specific mitochondrial therapeutic agents can help reduce symptoms and pain. This approach is expected to significantly improve the quality of life for patients. Individualized therapeutic approaches, on the other hand, are based on an in-depth assessment of the patient's degree of oxidative stress and mitochondrial functional status to develop a targeted treatment plan for more precise and effective IVDD management. Additionally, we suggest preventive measures like customized lifestyle changes and medications. These are based on understanding how IVDD develops. The aim is to slow down the disease and reduce the chances of it coming back. Actively promoting clinical trials and evaluating the safety and efficacy of new therapies helps translate cutting-edge treatment concepts into clinical practice. These measures not only improve patient outcomes and quality of life but also reduce the consumption of healthcare resources and the socio-economic burden, thus having a positive impact on the advancement of the IVDD treatment field.

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氧化应激在线粒体功能障碍中的作用及其对椎间盘退变的影响:机制与治疗策略
背景椎间盘退变(IVDD)被公认为腰痛的主要原因之一。椎间盘细胞是椎间盘(IVD)的主要组成部分,其功能包括合成和分泌胶原蛋白和蛋白多糖,以维持 IVD 的结构和功能稳定性。此外,IVD 细胞还参与多个生理过程。它们帮助维持 IVD 的营养代谢平衡。它们还具有抗氧化和抗炎作用。由于这些作用,IVD 细胞对 IVDD 至关重要。当 IVD 细胞受到氧化压力时,线粒体可能会受损,从而影响细胞的正常功能并加速退行性变化。线粒体是细胞的能量来源,并调节重要的细胞内过程。作为氧化还原反应的关键场所,过度的氧化应激和活性氧会损伤线粒体,导致炎症、DNA 损伤和细胞凋亡,从而加速椎间盘退变。全面探讨氧化应激、线粒体功能障碍和 IVDD 之间的复杂关系和潜在机制途径。突出潜在治疗靶点和前沿治疗概念。本文的转化潜力针对氧化应激和线粒体功能障碍的靶向治疗策略在 IVDD 的治疗中尤为关键。使用抗氧化剂和特定线粒体治疗剂有助于减轻症状和疼痛。这种方法有望大大改善患者的生活质量。另一方面,个体化治疗方法是在深入评估患者氧化应激程度和线粒体功能状态的基础上,制定有针对性的治疗计划,从而更精确、更有效地治疗 IVDD。此外,我们还建议采取预防措施,如改变生活方式和药物治疗。这些都是基于对 IVDD 发病过程的了解。这样做的目的是延缓病情发展,降低复发几率。积极推动临床试验,评估新疗法的安全性和有效性,有助于将前沿治疗理念转化为临床实践。这些措施不仅能改善患者的治疗效果和生活质量,还能减少医疗资源的消耗和社会经济负担,从而对 IVDD 治疗领域的发展产生积极影响。
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来源期刊
Journal of Orthopaedic Translation
Journal of Orthopaedic Translation Medicine-Orthopedics and Sports Medicine
CiteScore
11.80
自引率
13.60%
发文量
91
审稿时长
29 days
期刊介绍: The Journal of Orthopaedic Translation (JOT) is the official peer-reviewed, open access journal of the Chinese Speaking Orthopaedic Society (CSOS) and the International Chinese Musculoskeletal Research Society (ICMRS). It is published quarterly, in January, April, July and October, by Elsevier.
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