Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis
Synovial hypoxia as a cause of tendon rupture in rheumatoid arthritis
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DOI：
10.1016/j.jhsa.2007.09.002
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发表时间：
2008-01-01
影响因子：
1.9
通讯作者：
Kang, Norbert
中科院分区：
文献类型：
--
作者：
Sivakumar, Branavan;Akhavani, Mohammed A.;Kang, Norbert
目的缺氧和血管生成现在被认为是类风湿关节炎（RA）关节破坏持续的重要事件。然而，在50%的RA患者中，该疾病还涉及肌腱周围滑膜组织的炎症，这与多次断裂和长期手功能预后不良有关。本研究的目的是确定缺氧和血管生成是否也可能在类风湿性关节炎肌腱疾病中起作用。方法采用微电极技术对选择性手部手术治疗RA的患者术中进行匹配的体内滑膜氧测量（侵入性和包封性腱鞘和关节滑膜）。除炎性滑膜炎外，接受选择性手外科手术的患者作为对照。同时，采集RA滑膜组织并进行血管内皮生长因子（VEGF）和缺氧诱导因子-2 α染色。在低氧（1% O-2）或常氧（21% O-2）条件下培养组织，研究缺氧对VEGF及其可溶性受体表达的影响，以及对关键细胞因子白细胞介素(IL)-6、IL-8、IL-10和趋化因子单核细胞趋化蛋白-1的影响。结果同一患者有创性腱鞘缺氧程度明显高于无创性腱鞘或关节滑膜。此外，RA患者的腱鞘比非RA患者的腱鞘更缺氧。这种缺氧伴随着VEGF和缺氧诱导因子-2 α的表达。使用体外关节滑膜细胞培养，VEGF表达上调被证明是这种体内缺氧的结果。此外，缺氧下调单核细胞趋化蛋白-1和免疫调节细胞因子IL-10的释放。结论缺氧是类风湿肌腱病的一个特征，对类风湿肌腱病的血管生成和炎症级联有不同的调节作用。
Purpose Hypoxia and angiogenesis are now recognized as being important events in the perpetuation of joint destruction in rheumatoid arthritis (RA). In 50% of patients with RA, however, the disease also involves inflammation of the synovial tissue surrounding the tendons, which is associated with multiple ruptures and poor prognosis for long-term hand function. The aim of this study was to determine whether hypoxia and angiogenesis may also play a role in RA tendon disease. Methods Matched in vivo synovial oxygen measurements (invasive and encapsulating tenosynovium and joint synovium) were taken intra operatively using a microelectrode technique in patients having elective hand surgery for RA. Patients having elective hand surgery for indications other than inflammatory synovitis were recruited as controls. In parallel, RA synovial tissue was harvested and stained for vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-2 alpha. Tissue was also cultured under either hypoxic (1% O-2) or normoxic (21% O-2) conditions to investigate the effect of hypoxia on the expression of VEGF and its soluble receptor, as well as on the key cytokines interleukin (IL)-6, IL-8, IL-10 and the chemokine monocyte chemoattractant protein-1. Results Invasive tenosynovium was observed to be significantly more hypoxic than either noninvasive tenosynovium or joint synovium in the same patients. Furthermore, RA tenosynovium was shown to be more hypoxic than tenosynovium in patients without RA. This hypoxia was accompanied by expression of VEGF and hypoxia-inducible factor-2 alpha. Using in vitro joint synovial cell cultures, upregulation of VEGF expression was shown to be a consequence of this in vivo hypoxia. Furthermore, hypoxia downregulated release of monocyte chemoattractant protein-1 and the immunoregulatory cytokine IL-10. Conclusions These data demonstrate that hypoxia is a feature of rheumatoid tendon disease and differentially regulates angiogenesis and the inflammatory cascade in RA.