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首页> 外文期刊>Arthritis and Rheumatism >Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis
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Active involvement of alarmins S100A8 and S100A9 in the regulation of synovial activation and joint destruction during mouse and human osteoarthritis

机译：Alarmins S100A8和S100A9在小鼠和人类骨关节炎期间积极参与滑膜激活和关节破坏的调节

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Objective To investigate whether alarmins S100A8 and S100A9 are involved in mediating cartilage destruction during murine and human osteoarthritis (OA). Methods Two different murine models of OA that differed in terms of synovial activation were compared. Cartilage destruction was measured histologically. Synovial biopsy and serum samples from OA patients were derived from the Cohort Hip and Cohort Knee (CHECK) patients with symptomatic early OA. Expression of mediators in the synovium was measured by reverse transcription-polymerase chain reaction analysis and immunolocalization. Results In collagenase-induced OA, which showed marked synovial activation, interleukin-1β was expressed at significant levels only during the early stages of disease, whereas S100A8 and S100A9 expression remained high for a prolonged period of time (up to day 21 after induction). In S100A9-knockout mice, we found a major impact of S100A8 and S100A9 on synovial activation (62% inhibition) and OA cartilage destruction (45-73% inhibition) as compared to wild-type controls. In contrast, in the surgically induced destabilized medial meniscus model, in which synovial involvement is scant, we found no role of S100A8 and S100A9 in the focal OA cartilage destruction. Examination of arthroscopic synovial biopsy samples from patients in the early symptomatic OA CHECK cohort revealed substantial levels of S100A8 and S100A9 messenger RNA and protein, which correlated significantly with synovial lining thickness, cellularity in the subintima, and joint destruction. Levels of S100A8/A9 serum protein were significantly enhanced (19%) at baseline in patients who had pronounced progression of joint destruction after 2 years. Conclusion Our data suggest that the S100A8 and S100A9 proteins are crucially involved in synovial activation and cartilage destruction during OA and that high levels may predict joint destruction in humans with OA.
机译：目的探讨警报蛋白S100A8和S100A9是否参与介导鼠类和人类骨关节炎（OA）的软骨破坏。方法比较两种滑膜激活不同的OA小鼠模型。通过组织学测量软骨破坏。 OA患者的滑膜活检和血清样本来自有症状早期OA的队列髋关节和队列膝盖（CHECK）患者。通过逆转录-聚合酶链反应分析和免疫定位来测量滑膜中介质的表达。结果在胶原酶诱导的OA中，其表现出明显的滑膜激活，白介素1β仅在疾病的早期才以明显的水平表达，而S100A8和S100A9的表达在一段较长的时间内仍保持高水平（诱导后直至第21天） 。在S100A9敲除小鼠中，与野生型对照相比，我们发现S100A8和S100A9对滑膜激活（抑制62％）和OA软骨破坏（抑制45-73％）有重大影响。相反，在手术诱发的不稳定的内侧半月板模型中，滑膜受累很少，我们发现S100A8和S100A9在OA局灶性软骨破坏中没有作用。对早期有症状OA CHECK队列患者的关节镜滑膜活检样品进行检查后发现，S100A8和S100A9信使RNA和蛋白质水平较高，这与滑膜衬里厚度，内膜下细胞增多和关节破坏显着相关。在2年后明显出现关节破坏进展的患者中，基线时S100A8 / A9血清蛋白水平显着提高（19％）。结论我们的数据表明S100A8和S100A9蛋白与OA期间的滑膜激活和软骨破坏至关重要，并且高水平可能预示OA人体的关节破坏。

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