Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
Osteoarthritis Cartilage. 2016 May;24(5):827-34. doi: 10.1016/j.joca.2015.12.004. Epub 2015 Dec 18.
To identify novel biomarker(s) for knee osteoarthritis (OA) using a metabolomics approach.
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).
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 × 10(-13)) with knee OA patients having on average 69 μM 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 μM 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.
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.
采用代谢组学方法鉴定膝骨关节炎（OA）的新型生物标志物。
我们采用两阶段病例对照研究设计。在禁食 8 小时后采集膝骨关节炎患者和健康对照者的血浆样本，并使用靶向代谢组学分析试剂盒进行代谢分析。线性回归用于鉴定 OA 的新型代谢标志物。采用接收者操作特征（ROC）分析评估诊断价值。对人软骨进行基因表达分析，以探讨新型 OA 标志物的潜在机制。
64 例膝骨关节炎患者和 45 例对照者纳入发现阶段，72 例膝骨关节炎患者和 76 例年龄和性别匹配的对照者纳入验证阶段。我们鉴定并确认了 6 种与膝骨关节炎显著相关的代谢物，其中精氨酸与膝骨关节炎的相关性最为显著（P < 3.5×10(-13)），膝骨关节炎患者的平均水平比对照组低 69 μM。ROC 分析显示，精氨酸的诊断价值最大，曲线下面积（AUC）为 0.984。精氨酸浓度的最佳截断值为 57 μM，具有 98.3%的灵敏度和 89%的特异性。OA 患者精氨酸的耗竭很可能是由于精氨酸向鸟氨酸途径的过度活跃，导致软骨修复和降解之间的失衡。
难治性膝骨关节炎患者精氨酸明显耗竭。需要在纵向研究中进一步研究精氨酸是否可以预测早期 OA 变化。
