title: Regulation of osteoarthritis by omega-3 (n-3) polyunsaturated fatty acids in a naturally occurring model of disease.
abstract: OBJECTIVE
  To examine effects of high omega-3 (n-3) polyunsaturated fatty acid (PUFA) diets on development of osteoarthritis (OA) in a spontaneous guinea pig model, and to further characterise pathogenesis in this model. Modern diets low in n-3 PUFAs have been linked with increases in inflammatory disorders, possibly including OA. However, n-3 is also thought to increases bone density, which is a possible contributing factor in OA. Therefore we aim to determine the net influence of n-3 in disease development.
  
  
  METHODS
  OA-prone Dunkin-Hartley (DH) Guinea pigs were compared with OA-resistant Bristol Strain-2s (BS2) each fed a standard or an n-3 diet from 10 to 30 weeks (10/group). We examined cartilage and subchondral bone pathology by histology, and biochemistry, including collagen cross-links, matrix metalloproteinases (MMPs), alkaline phosphatase, glycosaminoglycan (GAG), and denatured type II collagen.
  
  
  RESULTS
  Dietary n-3 reduced disease in OA-prone animals. Most cartilage parameters were modified by n-3 diet towards those seen in the non-pathological BS2 strain - significantly active MMP-2, lysyl-pyridinoline and total collagen cross-links - the only exception being pro MMP-9 which was lower in the BS2, yet increased with n-3. GAG content was higher and denatured type II lower in the n-3 group. Subchondral bone parameters in the DH n-3 group also changed towards those seen in the non-pathological strain, significantly calcium:phosphate ratios and epiphyseal bone density.
  
  
  CONCLUSIONS
  Dietary n-3 PUFA reduced OA in the prone strain, and most disease markers were modified towards those of the non-OA strain, though not all significantly so. Omega-3 did not increase markers of pathology in either strain.
authors: Matrix Biology, Div. VPII, University of Bristol, Veterinary School, Langford, Bristol BS40 5DU, UK.
authors: L
authors: L
authors: Knott
authors: N C
authors: NC
authors: Avery
authors: A P
authors: AP
authors: Hollander
authors: J F
authors: JF
authors: Tarlton
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D024022:Fibrillar Collagens / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006168:Guinea Pigs; D006614:Hindlimb / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008592:Menisci, Tibial / Q000187:drug effects / Q000473:pathology; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D015525:Fatty Acids, Omega-3; D024022:Fibrillar Collagens; D006025:Glycosaminoglycans; D000469:Alkaline Phosphatase; D020782:Matrix Metalloproteinases