title: Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Oklahoma School of Science and Mathematics, Oklahoma City, OK 73104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Cai
authors.affiliation: Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hutchison
authors.affiliation: Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
authors.forename: J
authors.initials: J
authors.lastname: Hudson
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Laboratories of Biomolecular Dynamics, Department of Physics, School of Science, Kitasato University, Kanazawa, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: N
authors.initials: N
authors.lastname: Komori
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Dean A McGee Eye Institute, Oklahoma City, OK 73104, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Brush
authors.affiliation: Dean A McGee Eye Institute, Oklahoma City, OK 73104, USA; Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Anderson
authors.affiliation: Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
authors.forename: W E
authors.initials: WE
authors.lastname: Sonntag
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: hiroyuki-matsumoto@ouhsc.edu.
authors.forename: H
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA; Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: Tim-Griffin@omrf.org.
authors.forename: T M
authors.initials: TM
authors.lastname: Griffin
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002358:Cartilage, Articular / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004042:Dietary Fats, Unsaturated / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3 / Q000097:blood*; D043371:Fatty Acids, Omega-6 / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D005260:Female; D008297:Male; D008822:Mice, Transgenic; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013583:Synovial Membrane / Q000473:pathology; D013977:Tibia / Q000473:pathology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D016207:Cytokines; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6
keywords: Cartilage; Fat-1 transgene; Inflammation; Polyunsaturated fatty acids; Subchondral bone; Synovitis