A Cai1, E Hutchison2, J Hudson2, Y Kawashima3, N Komori4, A Singh4, R S Brush5, R E Anderson6, W E Sonntag7, H Matsumoto8, T M Griffin9. 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.
OBJECTIVE: We evaluated the effect of a reduction in the systemic ratio of n-6:n-3polyunsaturated 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-1transgenic 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-1mice, respectively, compared to WT littermates. IL-6 and TNF-α levels were reduced modestly in Fat-1mice. 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: Timothy R Koves; Ping Li; Jie An; Takayuki Akimoto; Dorothy Slentz; Olga Ilkayeva; G Lynis Dohm; Zhen Yan; Christopher B Newgard; Deborah M Muoio Journal: J Biol Chem Date: 2005-08-03 Impact factor: 5.157
Authors: Carrie A Karvonen-Gutierrez; Siobán D Harlow; Jon Jacobson; Peter Mancuso; Yebin Jiang Journal: Ann Rheum Dis Date: 2013-04-10 Impact factor: 19.103
Authors: Robert A Mooney; Erik R Sampson; Jaclyn Lerea; Randy N Rosier; Michael J Zuscik Journal: Arthritis Res Ther Date: 2011-12-07 Impact factor: 5.156
Authors: Ana M Torres-Guzman; Carlos E Morado-Urbina; Perla A Alvarado-Vazquez; Rosa I Acosta-Gonzalez; Aracely E Chávez-Piña; Rosa M Montiel-Ruiz; Juan M Jimenez-Andrade Journal: Arthritis Res Ther Date: 2014-03-10 Impact factor: 5.156
Authors: Yuanyuan Wang; Miranda L Davies-Tuck; Anita E Wluka; Andrew Forbes; Dallas R English; Graham G Giles; Richard O'Sullivan; Flavia M Cicuttini Journal: Arthritis Res Ther Date: 2009-05-08 Impact factor: 5.156
Authors: Yao Fu; Michael Kinter; Joanna Hudson; Kenneth M Humphries; Rachel S Lane; Jeremy R White; Michael Hakim; Yong Pan; Eric Verdin; Timothy M Griffin Journal: Arthritis Rheumatol Date: 2016-08 Impact factor: 10.995
Authors: Jong Min Park; Young Min Han; Migyeong Jeong; Eun Hee Kim; Weon Jin Ko; Joo Young Cho; Ki Baik Hahm Journal: J Gastroenterol Date: 2015-01-13 Impact factor: 7.527
Authors: A Batushansky; S Zhu; R K Komaravolu; S South; P Mehta-D'souza; T M Griffin Journal: Osteoarthritis Cartilage Date: 2021-09-17 Impact factor: 6.576
Authors: Adrián González-Alonso; César L Ramírez-Tortosa; Alfonso Varela-López; Enrique Roche; María I Arribas; M Carmen Ramírez-Tortosa; Francesca Giampieri; Julio J Ochoa; José L Quiles Journal: Int J Mol Sci Date: 2015-09-29 Impact factor: 5.923