骨关节炎相关病理改变的发病机制及治疗策略  

Pathogenesis and treatment strategies of osteoarthritis-related pathological changes

作　　者：文晨曦 李敬扬[1] WEN Chenxi;LI Jingyang(Zhuzhou Hospital Affiliated to Xiangya School of Medicine,Central South University,Zhuzhou 412000,China;XiangYa School of Medicine,Central South University,Changsha 410000,China)

机构地区：[1]中南大学湘雅医学院附属株洲医院风湿免疫科,株洲412000 [2]中南大学湘雅医学院,长沙410000

出　　处：《生命的化学》2021年第9期1974-1980,共7页Chemistry of Life

摘　　要：骨关节炎(osteoarthritis, OA)不同病理表现的发病机制不完全相同。其中,软骨下骨硬化及骨赘形成与软骨细胞的肥大分化相关,而Wnt/β-连环蛋白信号通路和hedgehog信号通路的相互关系在其中起到桥梁作用。本文介绍了软骨矿化在骨关节炎发病过程中的积极驱动作用,以及骨与软骨在发病过程中可能存在的动态反应差异。以M1巨噬细胞活化聚集为主要特征的滑膜炎是骨关节炎患者疼痛的主要原因,将其作为治疗靶点或能有效缓解OA症状。关节失稳包括软骨细胞对细胞外基质的失调和细胞外基质以SOX9为主要转录因子的合成代谢反应与分解代谢反应的失衡,前者依赖整合素信号传导,而包括缺氧诱导因子2-α、转化生长因子-β信号通路、Zinc-ZIP8-MTF1轴等在内的多种信号通路均通过促进分解代谢反应导致OA发病。其中金属硫蛋白对OA有双重作用,且两者相互独立。关于OA不同病理表现分子机制的研究对发现OA不同的治疗靶点具有重要意义。The pathogenesis of different pathological manifestations of osteoarthritis is not completely the same. Among them, subchondral bone sclerosis and osteophyte formation are related to the hypertrophy and differentiation of chondrocytes, and the correlation between the Wnt/β-catenin signaling pathway and the hedgehog signaling pathway serves as a bridge. Here we emphasizes the active driving role of cartilage mineralization in cell hypertrophy and differentiation, and the possible dynamic response differences between bone and cartilage in the pathogenesis. Synovitis characterized by activation and aggregation of M1 macrophages is the main cause of pain in patients with osteoarthritis, and it may be used as a therapeutic target to effectively alleviate the symptoms of OA. Joint instability includes the disorder of extracellular matrix by chondrocytes and the imbalance between the anabolic and catabolic responses of the extracellular matrix with SOX9 as the main transcription factor. The former relies on integrin signal transduction and includes hypoxia-inducible factor 2-α, TGF-β signaling pathway, metallothionein and many other signaling pathways all contributing to the onset of OA by promoting catabolic reactions;among them, metallothionein has a dual effect on OA, and the two are independent of each other. Research on the molecular mechanism of different pathological manifestations of OA is of great significance for discovering different therapeutic targets for OA.

关 键 词：骨关节炎 关节失稳 病理改变 发病机制 治疗靶点 

分 类 号：R684.3[医药卫生—骨科学]