Correlation network analysis shows divergent effects of a long-term,high-fat diet and exercise on early stage osteoarthritis phenotypes in mice  

作　　者：Timothy M.Griffin Albert Batushansky Joanna Hudson Erika Barboza Prado Lopes 

机构地区：[1]Aging and Metabolism Research Program,Oklahoma Medical Research Foundation(OMRF),Oklahoma City,OK 73104,USA [2]Reynolds Oklahoma Center on Aging and Departments of Biochemistry and Molecular Biology,Physiology,and Geriatric Medicine,University of Oklahoma Health Sciences Center,Oklahoma City,OK 73104,USA

出　　处：《Journal of Sport and Health Science》2020年第2期119-131,共13页运动与健康科学（英文）

基　　金：supported by the National Institutes of Health(P20RR018758,P20GM103441,P30GM114731,R03AR066828,and R01AG049058 to Dr.Griffin);the Arthritis Foundation(Arthritis Investigator Award to Dr.Griffin)。

摘　　要：Background:Obesity increases knee osteoarthritis(OA) risk through metabolic,inflammatory,and biomechanical factors,but how these systemic and local mediators interact to drive OA pathology is not well understood.We tested the effect of voluntary running exercise after chronic diet-induced obesity on knee OA-related cartilage and bone pathology in mice.We then used a correlation-based network analysis to identify systemic and local factors associated with early-stage knee OA phenotypes among the different diet and exercise groups.Methods:Male C57 BL/6 J mice were fed a defined control(10% kcal fat) or high fat(HF)(60% kcal fat) diet from 6 to 37 weeks of age.At 25 weeks,one-half of the mice from each diet group were housed in cages with running wheels for the remainder of the study.Histology,micro computed tomography,and magnetic resonance imaging were used to evaluate changes in joint tissue structure and OA pathology.These local variables were then compared to systemic metabolic(body mass,body fat,and glucose tolerance),inflammatory(serum adipokines and inflammatory mediators),and functional(mechanical tactile sensitivity and grip strength) outcomes using a correlation-based network analysis.Diet and exercise effects were evaluated by two-way analysis of variance.Results:An HF diet increased the infrapatellar fat pad size and posterior joint osteophytes,and wheel running primarily altered the subchondral cortical and trabecular bone.Neither HF diet nor exercise altered average knee cartilage OA scores compared to control groups.However,the coefficient of variation was≥25% for many outcomes,and some mice in both diet groups developed moderate OA(>33% maximum score).This supported using correlation-based network analyses to identify systemic and local factors associated with early-stage knee OA phenotypes.In wheel-running cohorts,an HF diet reduced the network size compared to the control diet group despite similar running distances,suggesting that diet-induced obesity dampens the effects of exercise on systemicBackground:Obesity increases knee osteoarthritis(OA) risk through metabolic,inflammatory,and biomechanical factors,but how these systemic and local mediators interact to drive OA pathology is not well understood.We tested the effect of voluntary running exercise after chronic diet-induced obesity on knee OA-related cartilage and bone pathology in mice.We then used a correlation-based network analysis to identify systemic and local factors associated with early-stage knee OA phenotypes among the different diet and exercise groups.Methods:Male C57 BL/6 J mice were fed a defined control(10% kcal fat) or high fat(HF)(60% kcal fat) diet from 6 to 37 weeks of age.At 25 weeks,one-half of the mice from each diet group were housed in cages with running wheels for the remainder of the study.Histology,micro computed tomography,and magnetic resonance imaging were used to evaluate changes in joint tissue structure and OA pathology.These local variables were then compared to systemic metabolic(body mass,body fat,and glucose tolerance),inflammatory(serum adipokines and inflammatory mediators),and functional(mechanical tactile sensitivity and grip strength) outcomes using a correlation-based network analysis.Diet and exercise effects were evaluated by two-way analysis of variance.Results:An HF diet increased the infrapatellar fat pad size and posterior joint osteophytes,and wheel running primarily altered the subchondral cortical and trabecular bone.Neither HF diet nor exercise altered average knee cartilage OA scores compared to control groups.However,the coefficient of variation was≥25% for many outcomes,and some mice in both diet groups developed moderate OA(>33% maximum score).This supported using correlation-based network analyses to identify systemic and local factors associated with early-stage knee OA phenotypes.In wheel-running cohorts,an HF diet reduced the network size compared to the control diet group despite similar running distances,suggesting that diet-induced obesity dampens the effects of exercise on systemic

关 键 词：Inflammation KNEE Mouse Obesity Wheel running 

分 类 号：R684.3[医药卫生—骨科学] R589.2[医药卫生—外科学]