College of Exercise and Health, Shenyang Sport University, Shenyang 110100, China.
Faculty of Physical Education, Tomsk State University, Tomsk 634050, Russia.
Biomed Pharmacother. 2024 May;174:116570. doi: 10.1016/j.biopha.2024.116570. Epub 2024 Apr 9.
Copper is an essential trace element in the human body that is extensively distributed throughout various tissues. The appropriate level of copper is crucial to maintaining the life activities of the human body, and the excess and deficiency of copper can lead to various diseases. The copper levels in the human body are regulated by copper homeostasis, which maintains appropriate levels of copper in tissues and cells by controlling its absorption, transport, and storage. Cuproptosis is a distinct form of cell death induced by the excessive accumulation of intracellular copper. Copper homeostasis and cuproptosis has recently elicited increased attention in the realm of human health. Cuproptosis has emerged as a promising avenue for cancer therapy. Studies concerning osteoarticular diseases have elucidated the intricate interplay among copper homeostasis, cuproptosis, and the onset of osteoarticular diseases. Copper dysregulation and cuproptosis cause abnormal bone and cartilage metabolism, affecting related cells. This phenomenon assumes a critical role in the pathophysiological processes underpinning various osteoarticular diseases, with implications for inflammatory and immune responses. While early Cu-modulating agents have shown promise in clinical settings, additional research and advancements are warranted to enhance their efficacy. In this review, we summarize the effects and potential mechanisms of copper homeostasis and cuproptosis on bone and cartilage, as well as their regulatory roles in the pathological mechanism of osteoarticular diseases (e.g., osteosarcoma (OS), osteoarthritis (OA), and rheumatoid arthritis (RA)). We also discuss the clinical-application prospects of copper-targeting strategy, which may provide new ideas for the diagnosis and treatment of osteoarticular diseases.
铜是人体必需的微量元素，广泛分布于各种组织中。铜的适当水平对维持人体的生命活动至关重要，而铜的过多和缺乏会导致各种疾病。人体铜水平通过铜动态平衡来调节，通过控制其吸收、运输和储存来维持组织和细胞中适当的铜水平。铜死亡是一种由细胞内铜过度积累引起的独特的细胞死亡形式。铜动态平衡和铜死亡最近在人类健康领域引起了更多的关注。铜死亡已成为癌症治疗的一种有前途的方法。有关骨关节炎疾病的研究阐明了铜动态平衡、铜死亡和骨关节炎疾病发病之间的复杂相互作用。铜失调和铜死亡导致骨和软骨代谢异常，影响相关细胞。这一现象在各种骨关节炎疾病的病理生理过程中起着关键作用，对炎症和免疫反应有影响。虽然早期的 Cu 调节剂在临床环境中表现出了一定的疗效，但仍需要进一步的研究和进展来提高其疗效。在这篇综述中，我们总结了铜动态平衡和铜死亡对骨和软骨的影响及其潜在机制，以及它们在骨关节炎疾病（如骨肉瘤（OS）、骨关节炎（OA）和类风湿关节炎（RA））病理机制中的调节作用。我们还讨论了铜靶向策略的临床应用前景，这可能为骨关节炎疾病的诊断和治疗提供新的思路。
