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中华关节外科杂志(电子版) ›› 2024, Vol. 18 ›› Issue (03) : 352 -362. doi: 10.3877/cma.j.issn.1674-134X.2024.03.008

综述

基于骨关节炎软骨细胞表型转化的新兴治疗靶点
张刚1, 秦勇2, 黄超2, 薛震2, 吕松岑2,()   
  1. 1. 150086 哈尔滨医科大学附属第二医院关节与运动医学外科;150010 哈尔滨市第一医院骨科
    2. 150086 哈尔滨医科大学附属第二医院关节与运动医学外科
  • 收稿日期:2024-01-02 出版日期:2024-06-01
  • 通信作者: 吕松岑
  • 基金资助:
    2022年“新时代龙江优秀硕士、博士论文”资助项目(LJYXL2022-071); 2021年度国家骨科与运动康复临床医学研究中心(2021-NCRC-CXJJ-PY-20)

Emerging therapeutic targets based on phenotypic transformation of osteoarthritic chondrocytes

Gang Zhang1, Yong Qin2, Chao Huang2, Zhen Xue2, Songcen Lyu2,()   

  1. 1. Department of Joint and Sports Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China;Department of Orthopedics, Harbin First Hospital, Harbin 150010, China
    2. Department of Joint and Sports Medicine, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China
  • Received:2024-01-02 Published:2024-06-01
  • Corresponding author: Songcen Lyu
引用本文:

张刚, 秦勇, 黄超, 薛震, 吕松岑. 基于骨关节炎软骨细胞表型转化的新兴治疗靶点[J/OL]. 中华关节外科杂志(电子版), 2024, 18(03): 352-362.

Gang Zhang, Yong Qin, Chao Huang, Zhen Xue, Songcen Lyu. Emerging therapeutic targets based on phenotypic transformation of osteoarthritic chondrocytes[J/OL]. Chinese Journal of Joint Surgery(Electronic Edition), 2024, 18(03): 352-362.

骨关节炎(OA)是导致关节疼痛与功能障碍的主要疾病之一。OA的病理改变主要是软骨细胞的变性。自噬和凋亡是软骨细胞维持内稳态的重要机制,在OA中发挥着至关重要的作用。氧化应激在调节OA软骨细胞凋亡和自噬方面发挥着重要作用。在OA中,软骨细胞的衰老会导致关节软骨退变,加速疾病的进展。由于代谢失衡和软骨细胞功能异常,软骨细胞表型从稳定状态转变为肥大状态,基质金属蛋白酶水平增加,最终导致软骨细胞的永久性损伤。随着OA的进展,软骨细胞表型也会相应地发生改变,不同表型的细胞在形态和功能方面都会有显著差异。OA是一种异质性关节紊乱,目前仍缺乏有临床转化价值的药物问世。本文总结了近年来关于OA发病机制中软骨细胞的表型转化及相关治疗靶点的新进展,为未来在临床上调节软骨细胞表型转化和更有效地治疗OA提供新策略。

Osteoarthritis (OA) is one of the major diseases that cause joint pain and dysfunction.The pathological changes of OA mainly focus on apoptosis and dysfunction of chondrocytes. Autophagy and apoptosis are important mechanisms for maintaining homeostasis of chondrocytes and play a crucial role in OA. Oxidative stress plays an important role in regulating apoptosis and autophagy of OA chondrocytes. In OA, Aging of chondrocytes can lead to degeneration of articular cartilage. Due to metabolic imbalance and abnormal chondrocyte function, the chondrocyte phenotype transitions from a stable state to a hypertrophic state. This transition is accompanied by an increase in matrix metalloproteinase levels, ultimately resulting in permanent damage to chondrocytes. With the progression of OA, the chondrocyte phenotype will also change accordingly, and cells with different phenotypes will have significant differences in morphology and function. OA is a heterogeneous joint disorder, and there is still a lack of drugs with clinical translational value. This paper summarized the new progress in chondrocyte phenotype transformation and related therapeutic targets in the pathogenesis of OA in recent years, which may provide novel strategies for regulating chondrocyte phenotype transition and more effectively treating OA in the future.

图1 凋亡和自噬在OA(骨关节炎)发生发展中的作用
Figure 1 The role of autophagy and apoptosis in the development of OA
图2 肥大和衰老表型在OA(骨关节炎)发生发展中的作用
Figure 2 The development of hypertrophy and senescence phenotypes in chondrocytes
图3 不同的细胞及其表型参与OA的发病机制18
Figure 3 Diferent cells and their phenotypes participate in the pathogenesis of OA
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