Inflammation in osteoarthritis.
Inflammation in osteoarthritis.
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骨关节炎的炎症。
DOI：
10.1097/bor.0b013e328349c2b1
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发表时间：
2011-09
影响因子：
5.1
通讯作者：
Otero M
中科院分区：
文献类型：
--
作者：
Goldring MB;Otero M
本文综述了骨关节炎发病机制中新的应激诱导和促炎机制，特别关注滑膜炎的作用以及其他关节组织对导致疾病发生和进展以及不可逆软骨损伤的细胞事件的贡献。在过去的2年中的研究已经发现了新的途径，当激活时，导致正常静止的关节软骨细胞被激活，并经历表型转变，导致稳态的破坏，并最终导致促炎和分解代谢基因的异常表达。在动物模型和回收的人体组织中的研究表明，促炎因子可以由软骨细胞本身或由滑膜和其他周围组织产生，即使在没有明显炎症的情况下，并且多个途径集中在聚集蛋白聚糖酶和胶原酶，特别是MMP-13的上调上。特别关注滑膜炎在创伤后关节损伤中的作用，如关节撕裂，以及细胞周基质通过受体介导软骨细胞反应的保护作用，如盘状结构域受体-2和syndecan-4。本文综述了转录因子NF-κB、C/EBPβ、ETS、Runx 2和缺氧诱导因子-2 α等细胞内信号的最新研究进展，以及炎症因子、趋化因子、脂肪因子、Toll样受体配体、晚期糖基化终产物受体、CpG甲基化和microRNA对这些信号的调节作用。对不同模型中常见的、在人类骨关节炎中发生的、在不同起始和进展阶段影响骨关节炎疾病过程的介质和途径的进一步研究，将为我们提供靶向治疗的新方向。
This review focuses on the novel stress-induced and proinflammatory mechanisms underlying the pathogenesis of osteoarthritis, with particular attention to the role of synovitis and the contributions of other joint tissues to cellular events that lead to the onset and progression of the disease and irreversible cartilage damage. Studies during the past 2 years have uncovered novel pathways that, when activated, cause the normally quiescent articular chondrocytes to become activated and undergo a phenotypic shift, leading to the disruption of homeostasis and ultimately to the aberrant expression of proinflammatory and catabolic genes. Studies in animal models and retrieved human tissues indicate that proinflammatory factors may be produced by the chondrocytes themselves or by the synovium and other surrounding tissues, even in the absence of overt inflammation, and that multiple pathways converge on the upregulation of aggrecanases and collagenases, especially MMP-13. Particular attention has been paid to the contribution of synovitis in posttraumatic joint injury, such as meniscal tears, and the protective role of the pericellular matrix in mediating chondrocyte responses through receptors, such as discoidin domain receptor-2 and syndecan-4. New findings about intracellular signals, including the transcription factors NF-κB, C/EBPβ, ETS, Runx2, and hypoxia-inducible factor-2α, and their modulation by inflammatory cytokines, chemokines, adipokines, Toll-like receptor ligands, and receptor for advanced glycation end-products, as well as CpG methylation and microRNAs, are reviewed. Further work on mediators and pathways that are common across different models and occur in human osteoarthritis and that impact the osteoarthritis disease process at different stages of initiation and progression will inform us about new directions for targeted therapies.