Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis

Osteoarthritis Cartilage. 2009 Jul;17(7):896-905. doi: 10.1016/j.joca.2008.12.009. Epub 2009 Jan 13.


Objective: To assess the relative efficacy of three different omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in suppressing the mRNA levels for important proteins involved in the etiology of osteoarthritis (OA).

Methods: A model cell culture system (bovine chondrocytes) was used. Inflammatory factors and enzymes involved in OA were induced by exposure of the chondrocyte cultures to interleukin-1alpha (IL-1alpha). The effect of pre-incubating cultures with various amounts of exogenous fatty acids on subsequent levels of mRNAs was assessed by reverse transcription-polymerase chain reactions (RT-PCR).

Results: Exposure of cultures to IL-1alpha induced expression of the cartilage proteinases A Disintegrin And Metalloproteinase with ThromboSpondin motifs (ADAMTS)-4 and ADAMTS-5, cyclooxygenase (COX)-2, the matrix metalloproteinase (MMP)-3 and the inflammatory cytokines IL-1alpha, interleukin-1beta (IL-1beta) and tumour necrosis factor-alpha (TNF-alpha). n-3 PUFAs were able to reduce the levels of mRNA for ADAMTS-4, ADAMTS-5, MMP-3, MMP-13, COX-2 (but not COX-1), IL-1alpha, IL-1beta and TNF-alpha. Eicosapentaenoic acid (EPA) was the most effective, followed by docosahexaenoic (DHA) and then alpha-linolenic (ALA) acid. The n-6 PUFA, arachidonic acid (AA) had no effect.

Conclusion: These results show that omega-3 (n-3) PUFAs cause a reduction in the mRNA levels for various proteins known to be important in the pathology of OA. They provide a molecular explanation, at least in part, for beneficial effects of dietary omega-3 PUFAs for the amelioration of symptoms of the disease. The relative efficacy of EPA suggests that this omega-3 PUFA may be especially useful for dietary supplementation in patients with OA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / metabolism
  • Animals
  • Carpus, Animal
  • Cartilage, Articular / metabolism
  • Cattle
  • Cells, Cultured
  • Chondrocytes / metabolism*
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Disease Models, Animal
  • Fatty Acids, Omega-3 / pharmacology*
  • Interleukin-1alpha / pharmacology
  • Lactic Acid / biosynthesis
  • Matrix Metalloproteinases / metabolism
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism*
  • Osteoarthritis / prevention & control
  • Peptide Hydrolases / metabolism*
  • RNA, Messenger / metabolism


  • Cytokines
  • Fatty Acids, Omega-3
  • Interleukin-1alpha
  • RNA, Messenger
  • Lactic Acid
  • Cyclooxygenase 2
  • Peptide Hydrolases
  • ADAM Proteins
  • Matrix Metalloproteinases