Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice

Osteoarthritis Cartilage. 2014 Sep;22(9):1301-9. doi: 10.1016/j.joca.2014.06.033. Epub 2014 Jul 4.


Objective: We evaluated the effect of a reduction in the systemic ratio of n-6:n-3 polyunsaturated fatty acids (PUFAs) on changes in inflammation, glucose metabolism, and the idiopathic development of knee osteoarthritis (OA) in mice. We hypothesized that a lower ratio of n-6:n-3 PUFAs would protect against OA markers in cartilage and synovium, but not bone.

Design: Male and female fat-1 transgenic mice (Fat-1), which convert dietary n-6 to n-3 PUFAs endogenously, and their wild-type (WT) littermates were fed an n-6 PUFA enriched diet for 9-14 months. The effect of gender and genotype on serum PUFAs, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and glucose tolerance was tested by 2-factor analysis of variance (ANOVA). Cortical and trabecular subchondral bone changes were documented by micro-focal computed tomography (CT), and knee OA was assessed by semi-quantitative histomorphometry grading.

Results: The n-6:n-3 ratio was reduced 12-fold and 7-fold in male and female Fat-1 mice, respectively, compared to WT littermates. IL-6 and TNF-α levels were reduced modestly in Fat-1 mice. However, these systemic changes did not reduce osteophyte development, synovial hyperplasia, or cartilage degeneration. Also the fat-1 transgene did not alter subchondral cortical or trabecular bone morphology or bone mineral density.

Conclusions: Reducing the systemic n-6:n-3 ratio does not slow idiopathic changes in cartilage, synovium, or bone associated with early-stage knee OA in mice. The anti-inflammatory and anti-catabolic effects of n-3 PUFAs previously reported for cartilage may be more evident at later stages of disease or in post-traumatic and other inflammatory models of OA.

Keywords: Cartilage; Fat-1 transgene; Inflammation; Polyunsaturated fatty acids; Subchondral bone; Synovitis.

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Biomarkers / metabolism
  • Blood Glucose / metabolism
  • Body Weight
  • Cartilage, Articular / pathology
  • Cytokines / blood
  • Dietary Fats, Unsaturated / therapeutic use*
  • Fatty Acids, Omega-3 / blood*
  • Fatty Acids, Omega-6 / administration & dosage
  • Fatty Acids, Omega-6 / blood*
  • Fatty Acids, Omega-6 / therapeutic use
  • Female
  • Male
  • Mice, Transgenic
  • Osteoarthritis / metabolism
  • Osteoarthritis / pathology
  • Osteoarthritis / prevention & control*
  • Synovial Membrane / pathology
  • Tibia / pathology


  • Biomarkers
  • Blood Glucose
  • Cytokines
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6