title: Metabolic profiling reveals differences in concentrations of oxylipins and fatty acids secreted by the infrapatellar fat pad of donors with end-stage osteoarthritis and normal donors.
abstract: OBJECTIVE
  The infrapatellar fat pad (IPFP) in the knee joint is hypothesized to contribute to osteoarthritis (OA) development by the IFPF possibly by influencing inflammatory processes. Oxylipins are essential mediators in the inflammatory process. We undertook this study to investigate secretion by the IFPF of fatty acids and oxylipins derived from those fatty acids.
  
  
  METHODS
  IPFP explants from 13 OA donors undergoing joint replacement surgery and from 10 normal donors postmortem were cultured for 24 hours, and supernatants (fat-conditioned medium [FCM]) were collected. Liquid chromatography tandem mass spectrometry detected fatty acids and oxylipins in FCM samples. Univariate and multivariate (partial least-squares discriminant analysis [PLS-DA]) analyses were performed, followed by pathway analysis. To validate these outcomes, a second set of OA FCM samples was measured (n=23).
  
  
  RESULTS
  Twenty-nine oxylipins and fatty acids could be detected in FCM. Univariate analysis showed no differences between normal donor and OA donor FCM; however, PLS-DA revealed an oxylipin/fatty acid profile consisting of 14 mediators associated with OA (accuracy rate 72%). The most important contributors to the model were lipoxin A4 (decreased), thromboxane B2 (increased), and arachidonic acid (increased). The statistical model predicted 64% of the second set of OA FCM samples correctly. Pathway analysis indicated differences in individual mediators rather than in complete pathways.
  
  
  CONCLUSIONS
  The IPFP secretes multiple and different oxylipins, and a subset of these oxylipins provides a distinctive profile for OA donors. It is likely that the observed changes are regulated by the OA process rather than being a consequence of basal metabolism changes, as an increase in fatty acid levels was not necessarily associated with an increase in oxylipins derived from that fatty acid.
authors.affiliation: The Netherlands Organization for Applied Scientific Research and Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: L M
authors.initials: LM
authors.lastname: Gierman
authors.forename: S
authors.initials: S
authors.lastname: Wopereis
authors.forename: B
authors.initials: B
authors.lastname: van El
authors.forename: E R
authors.initials: ER
authors.lastname: Verheij
authors.forename: B J C
authors.initials: BJ
authors.lastname: Werff-van der Vat
authors.forename: Y M
authors.initials: YM
authors.lastname: Bastiaansen-Jenniskens
authors.forename: G J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: V
authors.initials: V
authors.lastname: Stojanovic-Susulic
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: A-M
authors.initials: AM
authors.lastname: Zuurmond
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002853:Chromatography, Liquid / Q000379:methods; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D055442:Metabolome / Q000502:physiology*; D008875:Middle Aged; D015233:Models, Statistical; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D054883:Oxylipins / Q000378:metabolism*; D010329:Patella / Q000378:metabolism / Q000473:pathology; D015203:Reproducibility of Results; D012720:Severity of Illness Index; D053719:Tandem Mass Spectrometry / Q000379:methods; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D054883:Oxylipins