Objectives

This study aimed to determine possible associations between transcriptional and translational levels of clusterin (CLU) in the systemic and local joint environments with the severity of knee osteoarthritis (OA) and to investigate CLU mRNA expression in knee OA fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor-α.

Design

Circulating and synovial fluid CLU levels in 259 knee OA patients were quantified using an enzyme-linked immunosorbent assay. Relative CLU mRNA expression in 50 knee OA synovial tissues and 4 knee OA FLSs was determined using real-time polymerase chain reaction.

Results

Plasma CLU levels of knee OA patients were significantly higher than paired synovial fluid samples. Compared with early-stage knee OA patients, those with advanced-stage OA had considerably increased plasma and synovial fluid CLU levels. There were significant positive associations of plasma and synovial fluid CLU levels with radiographic severity of knee OA. Plasma CLU levels were directly correlated with its synovial fluid levels and high-sensitivity C-reactive protein levels in the patients. Receiver-operating characteristic curve analysis unveiled the potential utility of plasma CLU as a novel biomarker for knee OA severity (AUC = 0.80), with a sensitivity of 71.4% and a specificity of 73.3%. Marked upregulation of CLU mRNA expression was observed in both the inflamed synovial tissues and FLSs of knee OA.

Conclusion

Increased CLU mRNA and protein levels in the systemic and local joint environments of knee OA might reflect knee OA severity, especially systemic and synovial inflammation.

中文翻译：

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Clusterin 与膝关节骨性关节炎的全身性和滑膜炎症有关。

目标

本研究旨在确定全身和局部关节环境中聚簇蛋白 (CLU) 的转录和翻译水平与膝关节骨关节炎 (OA) 严重程度之间的可能关联，并研究受刺激的膝关节 OA 成纤维细胞样滑膜细胞 (FLS) 中CLU mRNA 的表达。与肿瘤坏死因子-α。

设计

使用酶联免疫吸附试验对 259 名膝关节 OA 患者的循环和滑液 CLU 水平进行了量化。使用实时聚合酶链反应测定 50 个膝关节 OA 滑膜组织和 4 个膝关节 OA FLS 中的相对CLU mRNA 表达。

结果

膝关节 OA 患者的血浆 CLU 水平显着高于配对的滑液样本。与早期膝关节 OA 患者相比，晚期 OA 患者的血浆和滑液 CLU 水平显着升高。血浆和滑液 CLU 水平与膝关节 OA 的放射学严重程度呈显着正相关。血浆 CLU 水平与其滑液水平和患者的高敏 C 反应蛋白水平直接相关。接受者操作特征曲线分析揭示了血浆 CLU 作为膝关节 OA 严重程度（AUC = 0.80）的新型生物标志物的潜在效用，敏感性为 71.4%，特异性为 73.3%。在发炎的滑膜组织和膝关节 OA 的 FLS 中均观察到CLU mRNA 表达的显着上调。

结论

膝关节 OA 全身和局部关节环境中 CLU mRNA 和蛋白质水平升高可能反映膝关节 OA 的严重程度，尤其是全身和滑膜炎症。