Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients
Metabolomic analysis of human plasma reveals that arginine is depleted in knee osteoarthritis patients
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DOI：
10.1016/j.joca.2015.12.004
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发表时间：
2016-05-01
影响因子：
7
通讯作者：
Zhai, G.
中科院分区：
文献类型：
--
作者：
Zhang, W.;Sun, G.;Zhai, G.
目的：利用代谢组学方法鉴定膝关节骨关节炎（OA）的新生物标志物。方法：采用两阶段病例对照研究设计。在禁食8小时后，收集膝关节OA患者和健康对照者的血浆样本，并使用靶向代谢组学测定试剂盒进行代谢谱分析。采用线性回归方法鉴定OA的新代谢标志物。采用受试者工作特征（ROC）分析来检验诊断价值。我们对人软骨进行了基因表达分析，以探索这种新型OA标志物的潜在机制。结果：64例膝关节OA患者和45例对照组被纳入发现阶段，72例膝关节OA患者和76例年龄和性别匹配的对照组被纳入验证阶段。我们鉴定并确认了6种与膝关节OA显著相关的代谢物，其中精氨酸是最显著的代谢物（P < 3.5 x 10(-13)），膝关节OA患者的平均M比对照组低69 μ M。ROC分析显示精氨酸的诊断价值最高，曲线下面积（AUC）为0.984。精氨酸浓度的最佳临界值为57 mM，灵敏度为98.3%，特异性为89%。OA患者精氨酸的消耗很可能是由于精氨酸对鸟氨酸通路的过度活跃，导致软骨修复和降解之间的不平衡。结论：在难治性膝关节炎患者中，精氨酸明显减少。需要进一步的纵向研究来检验精氨酸是否可以预测早期OA变化。(c) 2015年国际骨关节炎研究学会。Elsevier Ltd.出版。版权所有。
Objective: To identify novel biomarker(s) for knee osteoarthritis (OA) using a metabolomics approach.Method: We utilized a two-stage case-control study design. Plasma samples were collected from knee OA patients and healthy controls after 8-h fasting and metabolically profiled using a targeted metabolomics assay kit. Linear regression was used to identify novel metabolic markers for OA. Receiver operating characteristic (ROC) analysis was used to examine diagnostic values. Gene expression analysis was performed on human cartilage to explore the potential mechanism for the novel OA marker(s).Results: Sixty-four knee OA patients and 45 controls were included in the discovery stage and 72 knee OA patients and 76 age and sex matched controls were included in the validation stage. We identified and confirmed six metabolites that were significantly associated with knee OA, of which arginine was the most significant metabolite (P < 3.5 x 10(-13) ) with knee OA patients having on average 69 mu M lower than that in controls. ROC analysis showed that arginine had the greatest diagnostic value with area under the curve (AUC) of 0.984. The optimal cutoff of arginine concentration was 57 mM with 98.3% sensitivity and 89% specificity. The depletion of arginine in OA patients was most likely due to the over activity of arginine to ornithine pathway, leading to imbalance between cartilage repair and degradation.Conclusion: Arginine is significantly depleted in refractory knee OA patients. Further studies within a longitudinal setting are required to examine whether arginine can predict early OA changes. (c) 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.