中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (28): 4571-4576.doi: 10.12307/2023.585

• 组织构建综述 tissue construction review • 上一篇    下一篇

骨关节炎软骨细胞的新型程序性死亡

卢晓君1,熊波涵1,杨腾云1,王  旭2,张瑶璋1,钟瑞颖1,李彦林1   

  1. 1昆明医科大学第一附属医院运动医学科,云南省昆明市  650032;2昆明医科大学第二附属医院骨科,云南省昆明市  650032
  • 收稿日期:2022-09-19 接受日期:2022-11-08 出版日期:2023-10-08 发布日期:2023-01-29
  • 通讯作者: 李彦林,主任医师,教授,昆明医科大学第一附属医院运动医学科,云南省昆明市 650032
  • 作者简介:卢晓君,男,1998年生,江西省宜春市人,汉族,昆明医科大学运动医学在读硕士,主要从事软骨细胞程序性死亡的研究。
  • 基金资助:
    国家自然科学基金(81760403,81960409),项目负责人:李彦林;云南省陈世益专家工作站项目(2018IC102),项目负责人:李彦林;云南省骨关节疾病临床医学中心项目(ZX2019-03-04),项目负责人:李彦林

Novel programmed cell death of chondrocytes in osteoarthritis

Lu Xiaojun1, Xiong Bohan1, Yang Tengyun1, Wang Xu2, Zhang Yaozhang1, Zhong Ruiying1, Li Yanlin1   

  1. 1Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China; 2Department of Orthopedics, The Second Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
  • Received:2022-09-19 Accepted:2022-11-08 Online:2023-10-08 Published:2023-01-29
  • Contact: Li Yanlin, Chief physician, Professor, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
  • About author:Lu Xiaojun, Master candidate, Department of Sports Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
  • Supported by:
    National Natural Science Foundation of China, Nos. 81760403 and 81960409 (both to LYL); Chen Shiyi Expert Workstation Project of Yunnan Province, No. 2018IC102 (to LYL); Project of Clinical Medical Center for Bone and Joint Diseases of Yunnan Province, No. ZX2019-03-04 (to LYL)

摘要:

文题释义:

细胞焦亡:又称细胞炎性坏死,是一种程序性细胞死亡,表现为细胞不断胀大直至细胞膜破裂,导致细胞内容物的释放进而激活强烈的炎症反应。细胞焦亡是机体一种重要的天然免疫反应,在抗击感染中发挥重要作用。
坏死性凋亡:又叫程序性坏死,是一种受调控的由受体相互作用蛋白激酶1和受体相互作用蛋白激酶3介导的坏死性细胞死亡方式。坏死性凋亡的特征包括:细胞质膜完整性会在早期丢失,细胞内容物泄漏,以及细胞器肿胀。通过坏死性凋亡方式死亡的细胞缺乏典型的凋亡特征。
铁死亡:是一种铁依赖性的,区别于细胞凋亡、细胞坏死、细胞自噬的新型细胞程序性死亡方式。铁死亡的主要机制是:在二价铁或酯氧合酶的作用下,催化细胞膜上高表达的不饱和脂肪酸,发生脂质过氧化,从而诱导细胞死亡;此外,还表现为抗氧化体系(谷胱甘肽系统)的调控核心酶GPX4的降低。

背景:骨关节炎是一种常见的关节退行性疾病,其发生机制复杂,目前尚未阐明。但已有的研究表明,骨关节炎的发生发展与软骨细胞程序性死亡有关。
目的:总结骨关节炎软骨细胞新型程序性死亡的研究进展。
方法:“Osteoarthritis,Pyroptosis,Necroptosis,Ferroptosis,ROS,L-ROS,Iron-overload”为英文检索词,以“骨关节炎、细胞焦亡、坏死性凋亡、铁死亡、铁超载、脂质活性氧”为中文检索词,使用计算机在CNKI、万方数据库、PubMed、维普数据库检索2012年7月至2022年7月有关于程序性细胞死亡的相关文章,并进行系统地归纳、总结和分析。

结果与结论:焦亡与骨关节炎的关系近年来备受关注,目前的研究重点仍是NLRP3炎性小体和脂多糖。有关坏死性凋亡的研究中,骨关节炎的发展也已被证明与受体相互作用蛋白激酶1密切相关,受体相互作用蛋白激酶1有可能是治疗骨关节炎的潜在靶点。铁死亡是一种最新发现的细胞死亡方式,研究发现其通过铁超载和脂质过氧化介导了软骨细胞的死亡,但铁死亡的发生涉及多个基因的表达和调控,具有复杂的信号通路和机制,目前尚未完全阐明。细胞焦亡、坏死性凋亡和铁死亡在骨关节炎的发生发展中具有重要作用,但其相关通路、基因、miRNA仍需进一步研究。

https://orcid.org/ 0000-0001-9973-8723(卢晓君)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 骨关节炎, 程序性细胞死亡, 细胞焦亡, 坏死性凋亡, 铁死亡, 铁超载, 脂质过氧化

Abstract: BACKGROUND: Osteoarthritis is a common degenerative joint disease. Its pathogenesis is complex and has not been elucidated. However, studies have shown that the occurrence and development of osteoarthritis is related to the programmed death of chondrocytes. 
OBJECTIVE: To summarize the research progress in new programmed cell death in osteoarthritis chondrocytes.  
METHODS: “Osteoarthritis, Pyroptosis, Necroptosis, Ferroptosis, ROS, L-ROS, iron-overload” were used as English and Chinese search terms. Relevant articles on programmed cell death were searched in CNKI, WanFang, VIP, and PubMed. The search time was from July 2012 to July 2022. All included articles were summarized, concluded, and analyzed.
RESULTS AND CONCLUSION: The relationship between pyroptosis and osteoarthritis has attracted much attention in recent years, and current research still focuses on NLRP3 inflammasome and lipopolysaccharides. The development of osteoarthritis has also been shown to be closely associated with receptor-interacting protein kinase 1 in studies concerning necroptosis, and receptor-interacting protein kinase 1 could be a potential target for the treatment of osteoarthritis. Ferroptosis is a recently discovered mode of cell death, which has been found to mediate chondrocyte death through iron overload and lipid peroxidation, but ferroptosis involves the expression and regulation of multiple genes via complex signaling pathways and mechanisms that are not yet fully elucidated. Pyroptosis, necroptosis, and ferroptosis have important roles in the occurrence and development of osteoarthritis, but their related pathways, genes, and miRNAs still need further study.

Key words: osteoarthritis, programmed cell death, pyroptosis, necroptosis, ferroptosis, iron overload, lipid peroxidation

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