title: Targeted lipidomics reveals activation of resolution pathways in knee osteoarthritis in humans.
abstract: To investigate the presence of inflammation and resolution pathways in osteoarthritis (OA).
  
  
  
  Tissues were obtained from knee OA patients and control rheumatoid arthritis (RA) patients. Cells in synovial fluid (SF) were visualized by flow cytometry. Cytokines and chemokines were measured by multiplex assay. Lipid mediators (LMs) were determined by targeted lipidomics using liquid-chromatography mass spectrometry.
  
  
  
  SF of OA patients contained less cells, especially neutrophils, less cytokines and comparable levels of chemokines compared to RA controls. Thirty-seven lipids were detected in the soluble fraction of SF, including polyunsaturated fatty acids (PUFAs) and their pro-inflammatory and pro-resolving lipoxygenase (LOX) and cyclooxygenase (COX) pathway markers in both OA and RA patients. Among these, pro-inflammatory LM such as prostaglandin E2(PGE2) and thromboxane B2, as well as precursors and pathway markers of resolution such as 17-HDHA and 18-HEPE were detected. Interestingly, the pro-resolving lipid RvD2 could also be detected, but only in the insoluble fraction (cells and undigested matrix). Ratios of metabolites to their precursors indicated a lower activity of 5-LOX and 15-LOX in OA compared to RA, with no apparent differences in COX-derived products. Interestingly, synovial tissue and SF cells could produce 5-LOX and 15-LOX metabolites, indicating these cells as possible source of LM.
  
  
  
  By using a state-of-the-art technique, we show for the first time that resolution pathways are present in OA patients. A better understanding of these pathways could guide us to more effective therapeutic approaches to inhibit inflammation and further structural damage in OA and RA.
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands; Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: H.S.Jonasdottir@lumc.nl.
authors.forename: H S
authors.initials: HS
authors.lastname: Jónasdóttir
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: H.Brouwers@lumc.nl.
authors.forename: H
authors.initials: H
authors.lastname: Brouwers
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: J.C.Kwekkeboom@lumc.nl.
authors.forename: J C
authors.initials: JC
authors.lastname: Kwekkeboom
authors.affiliation: Department of Orthopedics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: H.M.J.van_der_linden@lumc.nl.
authors.forename: H M J
authors.initials: HMJ
authors.lastname: van der Linden
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: T.W.J.Huizinga@lumc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Huizinga
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: G.Kloppenburg@lumc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: R.E.M.Toes@lumc.nl.
authors.forename: R E M
authors.initials: REM
authors.lastname: Toes
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: M.A.Giera@lumc.nl.
authors.forename: M
authors.initials: M
authors.lastname: Giera
authors.affiliation: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: A.Ioan@lumc.nl.
authors.forename: A
authors.initials: A
authors.lastname: Ioan-Facsinay
mesh_terms: D016022:Case-Control Studies; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids / Q000032:analysis*; D020370:Osteoarthritis, Knee / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry* / Q000166:cytology
chemical_list: D018925:Chemokines; D016207:Cytokines; D008055:Lipids
keywords: Inflammation; Lipid mediators; Osteoarthritis; Resolution; Rheumatoid arthritis