Relative efficacies of omega-3 polyunsaturated fatty acids in reducing expression of key proteins in a model system for studying osteoarthritis.
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.
Zainal
Z
Z
School of Biosciences, Cardiff University, Cardiff, UK.
Longman
A J
AJ
Hurst
S
S
Duggan
K
K
Caterson
B
B
Hughes
C E
CE
Harwood
J L
JL
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
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