铜死亡在骨关节炎的作用

The role of cuproptosis in osteoarthritis

摘要:

骨关节炎（osteoarthritis, OA）是一种常见的退行性疾病，其特征是软骨变性、骨碎片形成、软骨下骨重塑和滑膜炎症。OA 早期大多采用药物、减肥等治疗，病情加重后，则需手术治疗。铜死亡（cuproptosis）是近期提出的一种新型细胞死亡方式。铜可直接与三羧酸循环中的脂酰化组分结合，致使脂酰化蛋白质积累及铁硫簇蛋白丢失，从而引起蛋白质毒性应激并最终导致细胞死亡。铜死亡的抑制可以影响各种与 OA 发展相关细胞的存活和增殖。本文通过总结铜死亡和调节铜死亡的关键基因与 OA 病理机制的联系及其对多种免疫细胞的影响，从而寻找治疗 OA 的新方法。

Abstract:

Osteoarthritis is a common degenerative disease characterized by cartilage degeneration, osteophyte formation, subchondral bone remodeling and synovial inflammation. Non-operative therapies, such as medications and weight control, are often adopted for the early stages of OA, whereas surgical treatment may be necessary if the condition worsened. Cuproptosis is a new cell death modality proposed recently, in which copper can directly bind to the fatty acylated components of the tricarboxylic acid cycle, resulting in the accumulation of fatty acylated proteins and the loss of iron sulfur tuftin, resulting in protein toxic stress and eventually cell death. Inhibition of cuproptosis can affect the survival and proliferation of various cells associated with OA development. In this paper, we summarize the relationship between cuproptosis and the key genes regulating cuproptosis and the pathological mechanism of OA and its effects on various immune cells, so as to find a new method for the treatment of OA