Background Pro-resolving lipid mediators (LM), such as resolvins, protectins and maresins, are powerful molecules that have a critical role in limiting inflammation and promoting tissue regeneration. Biochemically they are derived from the enzymatic oxygenation of poly-unsaturated fatty acids by lipoxygenases (LOX). Some LOX involved in the generation of pro-resolving LM have been suggested to play a role in the pathophysiology of osteoarthritis (OA) in humans (1,2). However, it is currently unclear whether pro-resolving pathways are activated in the osteoarthritic joint, as the presence of pro-resolving LM or their precursors was not yet investigated.
Objectives We aimed at investigating the presence and abundance of pro-resolving LM and their precursors in synovial fluid (SF) of OA patients compared to Rheumatoid Arthritis (RA) patients.
Methods SF samples from OA (n=8) and RA (n=9) patients visiting the outpatient clinic of the department of Rheumatology were collected. A targeted LC-MS (MS) lipidomics platform based on a QTrap mass spectrometer for the highly sensitive determination of several lipid mediators was used.
Results The presence of LM could be proven in 4 of the OA and 5 of the RA patient samples. The pro-resolving LM resolvin D5 and maresin 1 were readily detectable and were accompanied by the presence of pro-inflammatory mediators such as leukotriene B4 and anti-inflammatory LM, such as lipoxin A4 and B4. Notably, the pro-inflammatory prostaglandins E2 and D2 could be detected in only 1 OA sample, while they were present in all 5 RA samples. Hydroxy derivatives of polyunsaturated fatty acids (HETE, HEPE and HDHA) which are precursors and biomarkers for LM were additionally detected in both patient groups.
Conclusions This study indicates that a previously unrecognized pathway is likely activated in the knee joint of OA patients, as evidentiated by the presence of pro-resolving LM and their precursors in SF of these patients.
Arthritis Research & Therapy 2009, 11:R44
Arthritis Research & Therapy 2008, 10:R85
Disclosure of Interest None Declared
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