Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.
Application of global metabolomic profiling of synovial fluid for osteoarthritis biomarkers.
复制标题
DOI：
10.1016/j.bbrc.2018.03.117
复制
发表时间：
2018-05-05
影响因子：
3.1
通讯作者：
June RK
中科院分区：
文献类型：
--
作者：
Carlson AK;Rawle RA;Adams E;Greenwood MC;Bothner B;June RK
骨关节炎影响全球超过2.5亿人。目前，骨关节炎没有早期诊断的选择，这表明需要发现生物标志物。为了在人类滑液中发现骨关节炎的生物标志物，我们使用高效液相色谱质谱法进行全球代谢组学分析。从人骨关节炎（n=5）、类风湿性关节炎（n=3）和健康人（n=5）的滑液中提取代谢物，共检测到1233种代谢物。主成分分析清楚地区分了患病和健康滑液的代谢组学特征。类风湿性关节炎患者的滑液中含有与该疾病炎症性质相符的预期代谢物。同样，无监督聚类分析发现，每种疾病状态都与不同的代谢组学特征和共同调节的代谢物簇相关。对于骨关节炎，与健康滑液相比，共调节的代谢物上调，与已知的疾病过程相关，包括硫酸软骨素降解、精氨酸和脯氨酸代谢以及一氧化氮代谢。我们利用受者工作特征分析来确定每种代谢物的诊断价值，并鉴定出35种代谢物作为骨关节炎的潜在生物标志物，受者工作特征曲线下的面积为> 0.9。这些代谢物包括磷脂酰胆碱、溶血磷脂酰胆碱、神经酰胺、肉豆蔻酸衍生物和肉毒碱衍生物。这项初步研究为使用全球代谢组学对人类骨关节炎滑液进行更大规模的基于队列的研究提供了强有力的理由。这些数据的意义在于证明了滑液的代谢组学分析可以识别关节疾病的相关生物标志物。
Osteoarthritis affects over 250 million individuals worldwide. Currently, there are no options for early diagnosis of osteoarthritis, demonstrating the need for biomarker discovery. To find biomarkers of osteoarthritis in human synovial fluid, we used high performance liquid-chromatography mass spectrometry for global metabolomic profiling. Metabolites were extracted from human osteoarthritic (n=5), rheumatoid arthritic (n=3), and healthy (n=5) synovial fluid, and a total of 1233 metabolites were detected. Principal components analysis clearly distinguished the metabolomic profiles of diseased from healthy synovial fluid. Synovial fluid from rheumatoid arthritis patients contained expected metabolites consistent with the inflammatory nature of the disease. Similarly, unsupervised clustering analysis found that each disease state was associated with distinct metabolomic profiles and clusters of co-regulated metabolites. For osteoarthritis, co-regulated metabolites that were upregulated compared to healthy synovial fluid mapped to known disease processes including chondroitin sulfate degradation, arginine and proline metabolism, and nitric oxide metabolism. We utilized receiver operating characteristic analysis to determine the diagnostic value of each metabolite and identified 35 metabolites as potential biomarkers of osteoarthritis, with an area under the receiver operating characteristic curve > 0.9. These metabolites included phosphatidylcholine, lysophosphatidylcholine, ceramides, myristate derivatives, and carnitine derivatives. This pilot study provides strong justification for a larger cohort-based study of human osteoarthritic synovial fluid using global metabolomics. The significance of these data is the demonstration that metabolomic profiling of synovial fluid can identify relevant biomarkers of joint disease.
登录
查看更多内容
影响因子：
4.3
作者：
Cavill R;Kamburov A;Ellis JK;Athersuch TJ;Blagrove MS;Herwig R;Ebbels TM;Keun HC
通讯作者：
Keun HC
影响因子：
11.9
作者：
Hur M;Campbell AA;Almeida-de-Macedo M;Li L;Ransom N;Jose A;Crispin M;Nikolau BJ;Wurtele ES
通讯作者：
Wurtele ES
影响因子：
3.7
作者：
Kim S;Hwang J;Xuan J;Jung YH;Cha HS;Kim KH
通讯作者：
Kim KH
影响因子：
--
作者：
SHINMEI, M;MIYAUCHI, S;MIYAZAKI, K
通讯作者：
MIYAZAKI, K
影响因子：
7
作者：
Zhang, W.;Sun, G.;Zhai, G.
通讯作者：
Zhai, G.