1H NMR Metabolomics Identifies Underlying Inflammatory Pathology in Osteoarthritis and Rheumatoid Arthritis Synovial Joints

Despite osteoarthritis (OA) and rheumatoid arthritis (RA) being typically age-related, their underlying etiologies are markedly different. We used 1H nuclear magnetic resonance (NMR) spectroscopy to identify differences in metabolite profiles in low volumes of OA and RA synovial fluid (SF). SF was aspirated from knee joints of 10 OA and 14 RA patients. 100 μL SF was analyzed using a 700 MHz Avance IIIHD Bruker NMR spectrometer with a TCI cryoprobe. Spectra were analyzed by Chenomx, Bruker TopSpin and AMIX software. Statistical analysis was undertaken using Metaboanalyst. 50 metabolites were annotated, including amino acids, saccharides, nucleotides and soluble lipids. Discriminant analysis identified group separation between OA and RA cohorts, with 32 metabolites significantly different between OA and RA SF (false discovery rate (FDR) < 0.05). Metabolites of glycolysis and the tricarboxylic acid cycle were lower in RA compared to OA; these results concur with higher levels of inflammation, synovial proliferation and hypoxia found in RA compared to OA. Elevated taurine in OA may indicate increased subchondral bone sclerosis. We demonstrate that quantifiable differences in metabolite abundance can be measured in low volumes of SF by 1H NMR spectroscopy, which may be clinically useful to aid diagnosis and improve understanding of disease pathogenesis.

尽管骨关节炎（osteoarthritis, OA）与类风湿关节炎（rheumatoid arthritis, RA）通常均与年龄相关，但其潜在病因却存在显著差异。本研究采用氢质子核磁共振（1H nuclear magnetic resonance, 1H NMR）光谱技术，探究少量骨关节炎与类风湿关节炎滑膜液（synovial fluid, SF）的代谢谱差异。研究人员从10名骨关节炎患者与14名类风湿关节炎患者的膝关节中抽取滑膜液，取100 μL滑膜液，使用搭载TCI低温探头的700 MHz Avance IIIHD布鲁克（Bruker）核磁共振波谱仪开展分析。光谱数据通过Chenomx、布鲁克TopSpin及AMIX软件进行处理，统计分析则依托Metaboanalyst平台完成。本研究共注释得到50种代谢物，涵盖氨基酸、糖类、核苷酸及可溶性脂类。判别分析结果显示，骨关节炎与类风湿关节炎队列可实现明确分组分离，其中32种代谢物在两类滑膜液中存在显著差异（错误发现率（false discovery rate, FDR）< 0.05）。相较于骨关节炎患者，类风湿关节炎患者滑膜液内糖酵解与三羧酸循环相关代谢物水平更低，该结果与类风湿关节炎较骨关节炎更高的炎症水平、滑膜增生及缺氧状态相契合。骨关节炎患者滑膜液中牛磺酸水平升高，或提示软骨下骨硬化程度增加。本研究证实，通过氢质子核磁共振光谱技术可在微量滑膜液中定量检测代谢物丰度差异，该方法或可辅助临床诊断，并助力加深对疾病发病机制的理解。