Study [13-0245] study / subjects / design / samples / assays

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

Intervention/Observation study

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

Objective. The infrapatellar fat pad (IPFP) in the knee joint is hypothesized to contribute to osteoarthritis (OA) development possibly by influencing inflammatory processes. Oxylipins are essential mediators in the inflammatory process. We undertook this study to identify the secretion of fatty acids and oxylipins derived thereof by the IPFP. 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 leastsquares 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%). 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. Conclusion. The IPFP secretes multiple and different oxylipins, and a subset thereof provides a distinctive profile for OA donors. The observed changes are likely regulated by the OA process rather than 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.

13-0245

2013-08-15 00:00:00.0

Observational Human

Objective. The infrapatellar fat pad (IPFP) in the knee joint is hypothesized to contribute to osteoarthritis (OA) development possibly by influencing inflammatory processes. Oxylipins are essential mediators in the inflammatory process. We undertook this study to identify the secretion of fatty acids and oxylipins derived thereof by the IPFP.

not defined

Supplementary files.docx