A Lipidomic Study of Phospholipid Classes and Species in Human Synovial Fluid

Abstract

Objective. Membrane phospholipid species contribute to boundary lubrication that is provided by synovial fluid (SF). Altered levels of lubricants can be associated with increased friction, leading to articular cartilage damage. This study was undertaken to determine whether the composition of phospholipid species is altered in diseases of human knee joints.Methods. The study was performed using SF from unaffected controls and patients with early osteoarthritis (OA), late OA, or rheumatoid arthritis (RA). Lipids were extracted from cell-and vesicle-free SF from 9 control donors postmortem and from 17 patients with early OA, 13 patients with late OA, and 18 patients with RA. Phospholipid species were quantified by electrospray ionization tandem mass spectrometry.Results. We conducted lipidomic analysis to provide the first detailed overview of phospholipid species in human SF. We identified 130 lipid species belonging to 8 lipid classes (phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, plasmalogens, phosphatidylserine, phosphatidylglycerol, sphingomyelin, and ceramide). Compared to SF from controls, SF from patients with early OA and those with late OA had higher levels of most phospholipid species. Moreover, the concentrations of 64 and 27 phospholipids differed between RA and early OA SF and between RA and late OA SF, respectively. Also, the levels of 66 phospholipid species were altered in early OA versus late OA.Conclusion. Our data indicate disease-and stagedependent differences in the relative composition and levels of phospholipid species in human SF. Such alterations might affect articular joint lubrication. Because certain phospholipids scavenge reactive oxygen species (ROS) and are pro-or antiinflammatory, any altered phospholipid level might influence ROS-scavenging activity of SF and the inflammatory status of joints. Thus, phospholipids may be associated with the pathogenesis of OA.

Metabolomics in rheumatic diseases: desperately seeking biomarkers

“…A targeted lipidomics strategy was developed for quantification of anti-inflammatory bioactive fatty acids maresin 1, lipoxin A4 and resolvin D5. In a study of synovial fluid samples from unaffected controls ( n = 9) and from patients with early OA ( n = 17), late OA ( n = 13) or RA ( n = 30), phospholipid species were quantified by MS/MS 94 . Several lipid classes were identified, and the highest concentrations (with the exception of phosphatidylserine) were observed in late OA 94 .…”

“…In a study of synovial fluid samples from unaffected controls ( n = 9) and from patients with early OA ( n = 17), late OA ( n = 13) or RA ( n = 30), phospholipid species were quantified by MS/MS 94 . Several lipid classes were identified, and the highest concentrations (with the exception of phosphatidylserine) were observed in late OA 94 . Samples from patients with RA also had higher concentrations of these lipids than control samples.…”

Targeting the synovial angiogenesis as a novel treatment approach to osteoarthritis

“…A broad spectrum of cytokines, chemokines, ROS, lipids, lipidic mediators, complement pathway components and MMPs is secreted by activated SM cells and found to be increased in the synovial fluid of OA patients [Goldring et al 2011;Kosinska et al 2013;Ritter et al 2013]. Cytokines such as interleukin 1β (IL-1β), tumour necrosis factor-α (TNFα) and IL-6 have been largely investigated and presented as prominent cytokines in the pathogenesis of OA [McNulty et al 2013].…”

Choline kinase inhibition in rheumatoid arthritis

“…Other studies have also determined changes in phospholipid metabolites in serum of RA patients 9. The phospholipid composition of the synovial fluid (SF) has also been recently described 47. SF from patients with RA had higher content of total phospholipids, major phospholipid classes and phospholipid species than control SF.…”