中国组织工程研究

中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (17): 2723-2728.doi: 10.12307/2023.145

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

骨科相关疾病发生发展中的铁超载

黎  淼1，何  琪1，曾嘉旭1，陈柏豪1，黎少聪1，潘兆丰1，杨均政1，肖嘉聪1，王海彬2   

  1. 1广州中医药大学第一临床医学院，广东省广州市  510405；2广州中医药大学第一附属医院骨科，广东省广州市  510405
  • 收稿日期:2022-04-13 接受日期:2022-06-02 出版日期:2023-06-18 发布日期:2022-10-25
  • 通讯作者: 王海彬，博士，主任医师，广州中医药大学第一附属医院骨科，广东省广州市 510405
  • 作者简介:黎淼，男，1998年生，湖南省汨罗市人，汉族，广州中医药大学第一临床医学院在读硕士，主要从事骨质疏松症、骨与关节退行性疾病的研究。
  • 基金资助:
    国家自然科学基金资助项目(82074462)，项目负责人：王海彬；广州中医药大学“双一流”与高水平大学学科协同创新团队项目(2021xk53)，项目负责人：王海彬

Iron overload in bone diseases

Li Miao1, He Qi1, Zeng Jiaxu1, Chen Bohao1, Li Shaocong1, Pan Zhaofeng1, Yang Junzheng1, Xiao Jiacong1, Wang Haibin2   

  1. 1First Clinical Medicine School, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China; 2Department of Orthopedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Received:2022-04-13 Accepted:2022-06-02 Online:2023-06-18 Published:2022-10-25
  • Contact: Wang Haibin, MD, Chief physician, Department of Orthopedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • About author:Li Miao, Master candidate, First Clinical Medicine School, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, China
  • Supported by:
    the National Natural Science Foundation of China, No. 82074462 (to WHB); “Double First-class” and High-level University Discipline Collaborative Innovation Team Project of Guangzhou University of Chinese Medicine, No. 2021xk53 (to WHB)

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摘要：


文题释义：

铁超载：是指受血液性、遗传性疾病及年龄增长等因素的影响导致铁沉积，进而使组织损伤的一种典型的系统性疾病，多涉及内分泌器官(尤其是胰腺、性腺和脑垂体)、肝脏及心脏，与骨科疾病也具有一定相关性。
铁死亡：2012年DIXON等首次提出了铁死亡(ferroptosis)的概念，是一种依赖铁的、非凋亡的细胞死亡模式，并指出其特征是脂质活性氧的累积。

背景：铁是人体必需的金属，它的储存和运输机制复杂，且铁代谢平衡受多种因素的调节。当平衡被破坏时，机体发生铁超载会产生大量活性氧和细胞毒性，甚至引发细胞发生铁死亡进而导致组织器官的功能障碍。但目前关于铁超载的研究主要集中在心血管、神经系统和肿瘤疾病方面，而对于其导致的骨稳态平衡失调以及在骨相关疾病中的机制研究仍然有限。
目的：重点针对近年来铁超载在相关骨科疾病中的研究展开综述，并通过回顾铁超载在骨科疾病中的最新研究，为骨科相关疾病的治疗策略提供新思路。
方法：通过中文检索词“铁，铁超载，铁死亡，骨质疏松，骨关节炎，骨肿瘤，骨相关疾病”以及英文检索词“iron，iron overload，ferroptosis，osteoporosis，osteoarthritis，osteosarcoma，bone related diseases”在中国知网、万方数据库、PubMed、Web of Science 等平台进行检索，检索1978年1月至2022年1月的相关文献，共检索到文献1 085篇，根据入组标准，最终纳入文献79篇。
结果与结论：①铁超载引起的铁死亡在治疗骨科疾病中具有巨大潜力，但存在缺乏临床应用数据、未进入临床试验环节等问题；②铁超载引起铁死亡的研究集中于与铁结合产生活性氧的酶以及铁本身直接参与Fenton 反应介导活性氧积累；铁死亡作为一种独立的细胞死亡方式，为治疗这些疾病提供了一种新的方法，以及联合应用现有治疗方案的可能性，并有助于解决某些疾病的耐药性问题；③铁超载通过抑制成骨细胞活性和功能、促进破骨细胞分化和活化来参与骨质疏松症发展过程；铁超载可加速骨关节炎进展并促进软骨细胞凋亡及基质降解；铁超载能够诱导骨肉瘤细胞的铁死亡、凋亡和自噬，并抑制其侵袭能力；④铁超载引起铁死亡相关机制的研究为骨质疏松症、骨关节炎、骨肉瘤等骨科相关疾病治疗提供了新的靶点与方向。

https://orcid.org/0000-0003-1426-0607(黎淼)

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: 铁超载, 铁死亡, 骨质疏松, 骨关节炎, 骨肿瘤, 骨相关疾病

Abstract: BACKGROUND:  Iron is an essential metal for the human body. Its storage and transportation mechanism is complex, and various factors are involved in the balance of iron metabolism. When the metabolic balance is destroyed, iron overload in the body will produce a large number of reactive oxygen species and cytotoxicity and even lead to ferroptosis, resulting in functional dysfunction of tissues and organs. However, the current research on iron overload mainly focuses on cardiovascular, nervous system and tumor diseases, while the research on the imbalance of bone homeostasis caused by iron overload and its mechanism in bone diseases is still limited.
OBJECTIVE: To review the recent studies on iron overload in bone diseases and provides new ideas for the treatment of bone diseases by reviewing the latest findings of iron overload in bone diseases.
METHODS: The search terms “iron, iron overload, ferroptosis, osteoporosis, osteoarthritis, osteosarcoma, bone related diseases” in Chinese and English were used for the retrieval of literature published from January 1978 to January 2022 in CNKI, WanFang Database, PubMed, and Web of Science, respectively. A total of 1 085 articles were initially retrieved. According to the inclusion criteria, 79 articles were included for review.
RESULTS AND CONCLUSION: Ferroptosis caused by iron overload has great potential in the treatment of bone diseases, but there are some limitations such as lack of clinical application data and lack of clinical trials. Research on ferroptosis caused by iron overload focuses on the enzyme binding to iron to produce reactive oxygen species and irons that directly participate in Fenton reaction to mediate reactive oxygen species accumulation. Ferroptosis, as an independent form of cell death, offers a new approach to treating these diseases, as well as the possibility of combining existing treatment options and helping to address drug resistance in some diseases. Iron overload is involved in the development of osteoporosis by inhibiting the activity and function of osteoblasts and promoting the differentiation and activation of osteoclasts. Iron overload accelerates the progression of osteoarthritis and promotes chondrocyte apoptosis and matrix degradation. Iron overload can induce ferroptosis, apoptosis and autophagy of osteosarcoma cells and inhibit their invasion ability. Studies on the mechanism of ferroptosis caused by iron overload provide a new target and direction for the treatment of bone diseases such as osteoporosis, osteoarthritis, and osteosarcoma.

Key words: iron overload, ferroptosis, osteoporosis, osteoarthritis, osteosarcoma, bone diseases

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