Osteoarthritis (OA) is one of the costliest and most disabling forms of arthritis, and it poses a major public health burden; however, its detailed etiology, pathophysiology, and metabolism remain unclear. Therefore, the purpose of this study was to investigate the key plasma metabolites and metabolic pathways, especially focusing on radiographic OA severity and synovitis, from a large sample cohort study. We recruited 596 female volunteers who participated in the Iwaki Health Promotion Project in 2017. Standing anterior-posterior radiographs of the knee were classified by the Kellgren-Lawrence (KL) grade. Radiographic OA was defined as a KL grade of ≥ 2. Individual effusion-synovitis was scored according to the Whole-Organ Magnetic Resonance Imaging Scoring System. Blood samples were collected, and metabolites were extracted from the plasma. Metabolome analysis was performed using capillary electrophoresis time-of-flight mass spectrometry. To investigate the relationships among metabolites, the KL grade, and effusion-synovitis scores, partial least squares with rank order of groups (PLS-ROG) analyses were performed. Among the 82 metabolites examined in this assay, PLS-ROG analysis identified 42 metabolites that correlated with OA severity. A subsequent metabolite set enrichment analysis using the significant metabolites showed the urea cycle and tricarboxylic acid cycle as key metabolic pathways. Moreover, further PLS-ROG analysis identified cystine (p = 0.009), uric acid (p = 0.024), and tyrosine (p = 0.048) as common metabolites associated with both OA severity and effusion-synovitis. Receiver operating characteristic analyses showed that cystine levels were moderately associated with radiographic OA (p < 0.001, area under the curve 0.714, odds ratio 3.7). Large sample metabolome analyses revealed that cystine, an amino acid associated with antioxidant activity and glutamate homeostasis, might be a potential metabolic biomarker for radiographic osteoarthritis and early phase synovitis.

中文翻译：

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来自 Iwaki 健康促进项目的中年女性的放射性膝关节骨性关节炎和早期滑膜炎严重程度的代谢组学：一项横断面研究

骨关节炎 (OA) 是最昂贵和最致残的关节炎之一，它构成了重大的公共卫生负担；然而，其详细的病因、病理生理和代谢仍不清楚。因此，本研究的目的是从大样本队列研究中调查关键的血浆代谢物和代谢途径，特别是关注放射学 OA 严重程度和滑膜炎。我们招募了 596 名参与 2017 年 Iwaki 健康促进项目的女性志愿者。膝关节的站立前后位 X 光片按照 Kellgren-Lawrence (KL) 等级进行分类。放射学 OA 定义为 KL ≥ 2 级。根据全器官磁共振成像评分系统对个体渗出性滑膜炎进行评分。收集血样，并从血浆中提取代谢物。使用毛细管电泳飞行时间质谱法进行代谢组分析。为了研究代谢物、KL 分级和积液-滑膜炎评分之间的关​​系，进行了具有组排序的偏最小二乘法 (PLS-ROG) 分析。在该测定中检查的 82 种代谢物中，PLS-ROG 分析确定了 42 种与 OA 严重程度相关的代谢物。随后使用重要代谢物进行的代谢物集富集分析显示尿素循环和三羧酸循环是关键代谢途径。此外，进一步的 PLS-ROG 分析确定胱氨酸 (p = 0.009)、尿酸 (p = 0.024) 和酪氨酸 (p = 0.048) 是与 OA 严重程度和渗出性滑膜炎相关的常见代谢物。接受者操作特征分析显示，胱氨酸水平与影像学 OA 中度相关（p < 0.001，曲线下面积 0.714，优势比 3.7）。大样本代谢组分析显示，胱氨酸是一种与抗氧化活性和谷氨酸稳态相关的氨基酸，可能是放射学骨关节炎和早期滑膜炎的潜在代谢生物标志物。