Department of Biotechnology, Graduate School, Korea University, Seoul 02841, South Korea.
Department of Internal Medicine, National Police Hospital, Seoul 05715, South Korea.
Joint Bone Spine. 2017 Oct;84(5):605-610. doi: 10.1016/j.jbspin.2016.05.018. Epub 2016 Jul 25.
To investigate potential pathogenic pathways in the synovial fluid of osteoarthritis (OA) patients at different disease stages [early vs. late, determined based on the Kellgren-Lawrence (KL) grading scale], through metabolite profiles that were performed by using gas-chromatography/time-of-flight mass spectrometry (GC/TOF MS).
Synovial fluid samples were obtained from 15 patients with knee OA, divided into early- (KL grade: 1 and 2) and late-stage OA (KL grade: 3 and 4). Metabolite profiles of OA based on KL grading scale were performed using GC/TOF MS, with multivariate statistical analyses conducted by orthogonal partial least squares discriminant analysis (OPLS-DA) and hierarchical clustering analysis (HCA).
A total of 114 metabolites were identified and classified into various classes, such as amino acids, sugars and sugar alcohols, fatty acids, and organic acids. Significant discrimination of metabolite profiles between the early- and late-stage OA groups was shown by OPLS-DA and HCA. Twenty-eight metabolites, including malate, ethanolamine, squalene, glycerol, myristic acid, oleic acid, lanosterol, heptadecanoic acid, and capric acid, were identified as critical metabolites for discriminating between the early- and late-OA groups by using Student's t-test, as they showed significant differences in abundance between the two OA groups. These metabolites were related to fatty acid metabolism, glycerolipid metabolism, and the tricarboxylic acid cycle.
These results revealed that metabolite profiles are robustly altered along the radiographic stage of knee OA. Metabolomic approaches based on GC/TOF MS could provide valuable information on the underlying pathogenic mechanisms of OA progression.
通过气相色谱-飞行时间质谱（GC/TOF MS）分析，研究不同疾病阶段（基于 Kellgren-Lawrence [KL] 分级的早期与晚期）骨关节炎（OA）患者滑液中的潜在致病途径。
从 15 名膝关节 OA 患者中获得滑液样本，分为早期（KL 分级：1 和 2）和晚期 OA（KL 分级：3 和 4）。采用 GC/TOF MS 对基于 KL 分级的 OA 进行代谢物谱分析，通过正交偏最小二乘判别分析（OPLS-DA）和层次聚类分析（HCA）进行多变量统计分析。
共鉴定出 114 种代谢物，并分为各种类别，如氨基酸、糖和糖醇、脂肪酸和有机酸。OPLS-DA 和 HCA 显示早期和晚期 OA 组之间的代谢物谱存在显著差异。通过学生 t 检验，鉴定出 28 种代谢物，包括苹果酸、乙醇胺、角鲨烯、甘油、肉豆蔻酸、油酸、羊毛甾醇、十七烷酸和癸酸，作为区分早期和晚期 OA 组的关键代谢物，它们在两组 OA 中的丰度存在显著差异。这些代谢物与脂肪酸代谢、甘油脂质代谢和三羧酸循环有关。
这些结果表明，代谢物谱随着膝关节 OA 的放射学阶段而发生明显改变。基于 GC/TOF MS 的代谢组学方法可以为 OA 进展的潜在发病机制提供有价值的信息。
