Wheel Running Exacerbates Joint Damage after Meniscal Injury in Mice, but Does Not Alter Gait or Physical Activity Levels

Purpose: Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee osteoarthritis (OA). However, exercise has dose effects, with excessive exercise accelerating OA development and sedentary behaviors also promoting OA development. Prior work evaluating exercise in preclinical models has typically used prescribed exercise regimens; however, in-cage voluntary wheel running creates opportunities to evaluate how OA progression affects self-selected physical activity levels. This study aimed to evaluate how voluntary wheel running after a surgically induced meniscal injury affects gait characteristics and joint remodeling in C57Bl/6 mice. We hypothesize that injured mice will reduce physical activity levels as OA develops after meniscal injury and will engage in wheel running to a lesser extent than the uninjured animals.

Methods: Seventy-two C57Bl/6 mice were divided into experimental groups based on sex, lifestyle (physically active vs sedentary), and surgery (meniscal injury or sham control). Voluntary wheel running data were continuously collected throughout the study, and gait data were collected at 3, 7, 11, and 15 wk after surgery. At end point, joints were processed for histology to assess cartilage damage.

Results: After meniscal injury, physically active mice showed more severe joint damage relative to sedentary mice. Nevertheless, injured mice engaged in voluntary wheel running at the same rates and distances as mice with sham surgery. In addition, physically active mice and sedentary mice both developed a limp as meniscal injury progressed, yet exercise did not further exacerbate gait changes in the physically active mice, despite worsened joint damage.

Conclusions: Taken together, these data indicate a discordance between structural joint damage and joint function. Although wheel running after meniscal injury did worsen OA-related joint damage, physical activity did not necessarily inhibit or worsen OA-related joint dysfunction or pain in mice.