Abstract
Articular synovial fluid (SF) is a complex mixture of components that regulate nutrition, communication, shock absorption, and lubrication. Alterations in its composition can be pathogenic. This lipidomic investigation aims to quantify the composition of sphingolipids (sphingomyelins, ceramides, and hexosyl- and dihexosylceramides) and minor glycerophospholipid species, including (lyso)phosphatidic acid, (lyso)phosphatidylglycerol, and bis(monoacylglycero)phosphate species, in the SF of knee joints from unaffected controls and from patients with early (eOA) and late (lOA) stages of osteoarthritis (OA), and rheumatoid arthritis (RA).SF without cells and cellular debris from 9 postmortem donors (control), 18 RA, 17 eOA, and 13 lOA patients were extracted to measure lipid species using electrospray ionization tandem mass spectrometry - directly or coupled with hydrophilic interaction liquid chromatography.We provide a novel, detailed overview of sphingolipid and minor glycerophospholipid species in human SF. A total of 41, 48, and 50 lipid species were significantly increased in eOA, lOA, and RA SF, respectively when compared with normal SF.The level of 21 lipid species differed in eOA SF versus SF from lOA, an observation that can be used to develop biomarkers. Sphingolipids can alter synovial inflammation and the repair responses of damaged joints. Thus, our lipidomic study provides the foundation for studying the biosynthesis and function of lipid species in health and most prevalent joint diseases.
Highlights
Synovial fluid (SF) can be viewed as an ultrafiltrate of plasma that contains locally synthesized factors, such as cytokines; growth factors; and lubricating compounds, such as lubricin, hyaluronic acid, and phospholipids
Altered composition or concentrations of SF components are linked to osteoarthritis (OA) and rheumatoid arthritis (RA) [1,2,3]
SM 34:1 was the predominant species among SMs, accounting for 38% to 44% of total SMs in all cohorts (Figure 2)
Summary
Synovial fluid (SF) can be viewed as an ultrafiltrate of plasma that contains locally synthesized factors, such as cytokines; growth factors; and lubricating compounds, such as lubricin, hyaluronic acid, and phospholipids. Altered composition or concentrations of SF components are linked to osteoarthritis (OA) and rheumatoid arthritis (RA) [1,2,3]. A precise profile of the chemical composition of SF during diseaserelated alterations will increase our knowledge about the pathogenesis and possible options to treat these joint diseases. Sphingolipids (SLs) are a class of lipids that include ceramide (Cer) species, sphingomyelins (SMs) and more complex glycosphingolipids. A common constituent of all SLs is the sphingoid base, which is an organic aliphatic amino alcohol sphingosine (SPH) or a structurally similar compound [4]. The metabolic pathways of SLs form complex networks of reactions that involve many enzymes and intermediate metabolites that are needed for the biosynthesis, degradation, and remodeling of individual SLs [4,5,6]
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