Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis
Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis
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DOI：
10.1016/j.jchromb.2018.03.047
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发表时间：
2018-05-15
影响因子：
3
通讯作者：
Zhang, Xi
中科院分区：
文献类型：
--
作者：
Chen, Rui;Han, Su;Zhang, Xi
骨关节炎（OA）是一种退行性滑膜关节疾病，影响世界各地的人们。然而，OA的确切发病机制仍不清楚。进行代谢组学分析以深入了解OA的可能致病机制和诊断生物标志物。采用超高效液相色谱-三重四极杆质谱联用技术（UPLC-TQ-MS）测定32例OA患者和35例健康对照者血清氨基酸谱，并进行多元统计分析。使用项目值的变量重要性和学生t检验来确定OA中的代谢异常。另外30例OA患者作为独立样本，以验证氨基酸的改变。MetaboAnalyst用于识别关键氨基酸途径并构建描述其关系的代谢网络。UPLC-TQ-MS共检测到25种氨基酸和4种生物胺。健康对照组和OA患者之间的氨基酸谱存在差异。丙氨酸、γ-氨基丁酸和4-羟基-L-脯氨酸是区分OA患者和健康对照的重要生物标志物。影响最显著的代谢途径涉及丙氨酸、天冬氨酸、谷氨酸、精氨酸和脯氨酸的代谢。本研究结果有助于从分子水平上了解OA的氨基酸代谢异常和发病机制。代谢紊乱可能对OA的诊断和预防具有重要意义。
Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, gamma-aminobutyric acid and 4-hydroxy-L-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA.