title: Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Biosciences, Cardiff University, Cardiff, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Zainal
authors.forename: A J
authors.initials: AJ
authors.lastname: Longman
authors.forename: S
authors.initials: S
authors.lastname: Hurst
authors.forename: K
authors.initials: K
authors.lastname: Duggan
authors.forename: B
authors.initials: B
authors.lastname: Caterson
authors.forename: C E
authors.initials: CE
authors.lastname: Hughes
authors.forename: J L
authors.initials: JL
authors.lastname: Harwood
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000818:Animals; D002350:Carpus, Animal; D002358:Cartilage, Articular / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D053582:Interleukin-1alpha / Q000494:pharmacology; D019344:Lactic Acid / Q000096:biosynthesis; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D010447:Peptide Hydrolases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D019344:Lactic Acid; D051546:Cyclooxygenase 2; D010447:Peptide Hydrolases; D051722:ADAM Proteins; D020782:Matrix Metalloproteinases