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J Appl Physiol (1985). 2015 Mar 15;118(6):760-7. doi: 10.1152/japplphysiol.00112.2014. Epub 2015 Jan 15.

The beneficial effects of exercise on cartilage are lost in mice with reduced levels of ECSOD in tissues.

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Department of Medicine, National Jewish Health, Denver, Colorado;
Department of Medicine, Division of Geriatric Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado;
Department of Mechanical Engineering, University of Colorado, Denver, Colorado; and.
Department of Medicine, National Jewish Health, Denver, Colorado;
Department of Medicine, National Jewish Health, Denver, Colorado; Department of Biochemistry and Molecular Biology, University of Nebraska Health Sciences Center, Omaha, Nebraska.


Osteoarthritis (OA) is associated with increased mechanical damage to joint cartilage. We have previously found that extracellular superoxide dismutase (ECSOD) is decreased in OA joint fluid and cartilage, suggesting oxidant damage may play a role in OA. We explored the effect of forced running as a surrogate for mechanical damage in a transgenic mouse with reduced ECSOD tissue binding. Transgenic mice heterozygous (Het) for the human ECSOD R213G polymorphism and 129-SvEv (wild-type, WT) mice were exposed to forced running on a treadmill for 45 min/day, 5 days/wk, over 8 wk. At the end of the running protocol, knee joint tissue was obtained for histology, immunohistochemistry, and protein analysis. Sedentary Het and WT mice were maintained for comparison. Whole tibias were studied for bone morphometry, finite element analysis, and mechanical testing. Forced running improved joint histology in WT mice. However, when ECSOD levels were reduced, this beneficial effect with running was lost. Het ECSOD runner mice had significantly worse histology scores compared with WT runner mice. Runner mice for both strains had increased bone strength in response to the running protocol, while Het mice showed evidence of a less robust bone structure in both runners and untrained mice. Reduced levels of ECSOD in cartilage produced joint damage when joints were stressed by forced running. The bone tissues responded to increased loading with hypertrophy, regardless of mouse strain. We conclude that ECSOD plays an important role in protecting cartilage from damage caused by mechanical loading.


bone; cartilage; extracellular superoxide dismutase; osteoarthritis; running

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