LAUSR

PURPOSE Exercise and physical activity are recommended to reduce pain and improve joint function in patients with knee 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 aims to evaluate how voluntary wheel running following a surgically induced meniscal injury affects gait characteristics and joint remodeling in C57Bl/6 mice. We hypothesize injured mice will reduce physical activity levels as OA develops following 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 versus sedentary), and surgery (meniscal injury or sham control). Voluntary wheel running data was continuously collected throughout the study and gait data was collected at 3, 7, 11, and 15 weeks after surgery. At endpoint, joints were processed for histology to assess cartilage damage. RESULTS Following 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. Additionally, 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. While wheel running following meniscal injury did worsen OA-related joint damage, physical activity did not necessarily inhibit or worsen OA-related joint dysfunction or pain in mice.