Artikel
A lipidomic study of phospholipid classes and species in human synovial fluid
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Veröffentlicht: | 23. Oktober 2013 |
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Gliederung
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Objective: Membrane phospholipid (PL) species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants such as lubricin, hyaluronan and PL are associated with increased friction, leading to articular cartilage damage. The aim of our lipidomic study was to determine whether the composition of PL species correlates with diseases of human knee joints using SF from non-affected controls, early osteoarthritis (eOA), late OA, and rheumatoid arthritis (RA) patients.
Methods: Lipids were extracted from cell-, and vesicle-free SF of 9 post-mortem donors (control) and 17 eOA, 13 late OA, and 18 RA patients. PL classes and species were quantified by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Subsequently, the quantitative values of all PL species were corrected for possible dilution of SF according to the method described by Kraus et al (2002). This study was approved by the local ethics committee of Justus-Liebig-University Giessen, and all patients provided written informed consent. Statistically significant differences in PL concentrations between cohorts were analyzed by Kruskal-Wallis test. Adjustments for multiple testing in the series of Kruskal-Wallis tests were made to control the false discovery rate (FDR), which was set to 10%. Subsequently, the statistical significances of pair wise differences in median concentrations of PL species between cohorts were analyzed by Wilcoxon rank-sum test. P values of less than 0.05 were considered statistically significant.
Results and conclusion: By lipidomic analysis, we have provided the first detailed overview of PL species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramides). Compared to control SF, eOA and late OA had higher levels of most PL species. Moreover, the concentrations of 64 and 27 PLs modulated between RA and eOA respectively late OA SF. The levels of 66 PL species were significantly altered in eOA SF versus late OA.
Disease- and stage-dependent differences of PL species in SF alter articular joint lubrication. Increased levels of PLs during OA may constitute a response to enhance articular surface lubrication. Because certain PLs scavenge reactive oxygen species (ROS) and are pro- or anti-inflammatory, any altered PL level might influence ROS-scavenging activity of SF and the inflammatory status of joints. Thus, PLs mediate in part the pathogenesis of OA.