Development of a Mouse Model of Knee Osteoarthritis Based on Obesity and Bipedal Walking

To investigate the influence of obesity and obligatory bipedal walking on osteoarthritis (OA) development, 26-week-old C57BL/6 mice were divided into two groups and obesity was induced in one group with a 60% fat diet. After 8 weeks, mice from each group were again divided into two groups and obligatory bipedal exercise was induced with a specially designed treadmill in one group, resulting in four experimental groups (control, control bipedal, obese, and obese bipedal). After 8, 10, and 12 weeks of bipedal walking, knee joints were obtained and graded. Surface fibrillation and matrix proteoglycan depletion, began to appear after 8 weeks of exercise in the bipedal groups and progressed as the duration of the exercise increased. At 12 weeks, cartilage loss extending >75% of articular cartilage was observed in none of the control and obese groups, and in 42.8% and 77.7% of control bipedal and obese bipedal animals, respectively. OA grading was significantly higher in the obese bipedal group compared with the control bipedal group. The von Frey fiber test thresholds decreased significantly in the bipedal groups compared with the control and obese groups. This model can be used to study the pathogenesis of human OA and to evaluate its therapeutic agents. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2411-2419, 2019.