Voluntary Exercise and the Development of Osteoarthritis in Mice Fed a High-fat Diet

Abstract

Osteoarthritis (OA) is a progressive, degenerative joint disease characterized by an imbalance of articular cartilage biosynthesis and degradation attributed to both inflammatory and biomechanical factors. Obesity, or factors associated with obesity, are a primary risk factor for OA in both load-bearing and non-load bearing joints, suggesting that systemic factors mediate obesity-induced OA. PURPOSE: To test the hypothesis that voluntary exercise mitigates the development of OA in diet-induced obese mice. METHODS: 12-week old male mice (C57BL/6J) were fed either normal chow (NC) (n = 10) or high-fat (HF) chow (60% kcal fat) (n = 10). After 8 weeks of feeding, half the mice from each diet group were housed in cages equipped with a custom-designed running wheel that allowed for continuous monitoring of voluntary running activity. Mice continued to have free access to their respective diets during the exercise period. The study ended when the mice were 24 weeks old (i.e., after 4 weeks of exercise). Percent body fat was assessed using DEXA analysis. Knee joint degeneration was assessed using histomorphometric analysis following a modified Mankin OA scoring system developed for mice. RESULTS: HF feeding significantly increased body mass (HF: 37.9 ± 1.3 g, NC: 24.4 ± 0.35 g, P < 0.05), percent body fat (HF: 34.7 ± 2.1%, NC: 11.0 ± 0.44%, P < 0.05), and joint degeneration (HF: 18.2 ± 2.4, NC: 10.4 ± 2.1, P < 0.05) in non-exercised mice. Diet, however, did not affect the average daily running distance in exercised mice (HF: 6.15 ± 0.67 km/day, NC: 6.75 ± 0.70 km/day, P = 0.6). Contrary to our hypothesis, exercise did not affect joint degeneration in either the HF (18.2 ± 0.7, P = 0.75) or the NC (12.4 ± 2.0, P = 0.67) fed mice. Body mass and percent body fat were not affected by 4 weeks of voluntary exercise in either diet group. CONCLUSION: High-fat feeding is an effective means of inducing non-traumatic joint degeneration in mice at a relatively young age. Voluntary wheel running exercise did not affect the development of joint degeneration in the medial compartment of the knee joint. Our previous studies of HF diet-induced OA in mice indicate that joint degeneration is positively correlated with body mass and body fat. Thus, longer duration or higher intensity exercise that is sufficient to reduce body mass or fat levels may be needed to alter the pathogenesis of HF diet-induced OA in mice. Supported by NIH grants AR50245 and AR51672.