Local and systemic inflammatory lipid profiling in a rat model of osteoarthritis with metabolic dysregulation

PLoS One. 2018 Apr 23;13(4):e0196308. doi: 10.1371/journal.pone.0196308. eCollection 2018.

Abstract

Objective: Bioactive oxidised lipids (oxylipins) are important signalling mediators, capable of modulating the inflammatory state of the joint and anticipated to be of importance in joint homeostasis and status of osteoarthritis. The aim of this study was to quantify oxylipin levels in plasma and synovial fluid from rats with experimentally induced osteoarthritis to investigate the potential role of oxylipins as a marker in the disease process of early osteoarthritis.

Design: Forty rats were randomly allocated to a standard or high-fat diet group. After 12 weeks, local cartilage damage was induced in one knee joint in 14 rats of each diet group. The remaining 6 rats per group served as controls. At week 24, samples were collected. Oxylipin levels were quantified by liquid chromatography-mass spectrometry.

Results: Overall, 31 lipid-derived inflammatory mediators were detected in fasted plasma and synovial fluid. Principal component analysis identified four distinct clusters associated with histopathological changes. Diet induced differences were evident for 13 individual plasma oxylipins, as well as 5,6-EET in synovial fluid. Surgical-model induced differences were evident for three oxylipins in synovial fluid (15-HETE, 8,9-DHET and 17R-ResolvinD1) with a different response in lipid concentrations for synovial fluid and plasma.

Conclusions: We demonstrate the quantification of oxidised lipids in rat plasma and synovial fluid in a model of early experimental osteoarthritis. Oxylipins in the synovial fluid that were altered as consequence of the surgically induced osteoarthritis were not represented in the plasma. Our findings suggest differential roles of the oxylipins in the local versus peripheral compartment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Chromatography, Liquid
  • Disease Models, Animal
  • Inflammation / blood
  • Inflammation / metabolism
  • Inflammation Mediators / analysis*
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Knee Joint / metabolism
  • Knee Joint / pathology
  • Lipid Metabolism
  • Lipids / analysis*
  • Lipids / blood
  • Male
  • Metabolome
  • Osteoarthritis / blood
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology*
  • Oxylipins / analysis
  • Oxylipins / blood
  • Oxylipins / metabolism
  • Rats
  • Rats, Wistar
  • Synovial Fluid / chemistry*
  • Synovial Fluid / metabolism
  • Tandem Mass Spectrometry / methods

Substances

  • Biomarkers
  • Inflammation Mediators
  • Lipids
  • Oxylipins

Grants and funding

The research leading to these results has received partial funding from the European Union Seventh Framework Programme (FP7/2007–2013, https://cordis.europa.eu/project/rcn/105314_en.html) under grant agreement n°305815 to HW. The study was also supported by the Dutch Arthritis Foundation (LLP-22, https://home.reumafonds.nl/) to HW. Funding sources had no role in study design, collection, analysis or interpretation of the data, writing of the manuscript or in the decision to submit the manuscript for publication.