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Osteoarthritis Cartilage. 2014 Sep;22(9):1301-9. doi: 10.1016/j.joca.2014.06.033. Epub 2014 Jul 4.

Metabolic enrichment of omega-3 polyunsaturated fatty acids does not reduce the onset of idiopathic knee osteoarthritis in mice.

Author information

1
Oklahoma School of Science and Mathematics, Oklahoma City, OK 73104, USA.
2
Free Radical Biology and Aging Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
3
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.
4
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
5
Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Dean A McGee Eye Institute, Oklahoma City, OK 73104, USA.
6
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.
7
Department of Geriatric Medicine, Reynolds Oklahoma Center on Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
8
Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: hiroyuki-matsumoto@ouhsc.edu.
9
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.

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.

DESIGN:

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.

KEYWORDS:

Cartilage; Fat-1 transgene; Inflammation; Polyunsaturated fatty acids; Subchondral bone; Synovitis

PMID:
25008209
PMCID:
PMC4150746
DOI:
10.1016/j.joca.2014.06.033
[Indexed for MEDLINE]
Free PMC Article

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