Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model

Abstract

Objective The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate markers of functional impairment in relation to cartilage loss and pathological changes in a post-traumatic mouse model of OA. Method We performed a battery of functional analyses in a mouse model of OA generated by cruciate ligament transection (CLT). The changes in functional analyses were linked to histological changes graded by OARSI standards, histological grading of synovitis, and volumetric changes of the articular cartilage and osteophytes quantified by phase contrast micro-CT. Results OA generated by CLT led to decreased time on rotarod, delayed response on hotplate analysis, and altered gait starting from 4 weeks after surgery. Activity in open field analysis did not change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was directly correlated with higher OARSI histological scores of OA, synovitis in the knee joints, cartilage volume loss, and osteophyte formation. Conclusion Our findings link functional analyses to histological grading, synovitis, comprehensive 3-dimensional assessment of cartilage volume and osteophyte formation. This serves as a reference for a mouse model in predicting outcomes of OA treatment.

Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury

“…In humans, a study conducted with lean and obese individuals indicates similar levels of spontaneous physical activity 37. Furthermore, our result that spontaneous locomotion was independent of injury-induced OA is in agreement with recent findings using cruciate ligament transection OA model in mice 38. It has also been reported that recreational activities do not contribute to OA in normal and overweight individuals 39 40…”

Gait analysis methods for rodent models of arthritic disorders: reviews and recommendations

“…Stride length, step length, step width, and limb duty factor are highly correlated to walking speed; thus, accounting for velocity is absolutely essential 3, 35, 36 . This can be done through statistical models 8 , comparisons to controls 8–10, 25, 37 , or by controlling velocity with treadmill 29, 31, 38–40 . However, it should be noted treadmills can mask subtle spatiotemporal changes by inducing stress, and treadmill measurements vary significantly from open arena measurements 3 .…”

Animal Models of Meniscal Injury in Post-Traumatic Arthritis

“…The discrepancy between these studies may result from the length of time mice were assessed for spontaneous activity. However, when mice receive transection of both anterior and posterior cruciate ligament, they showed decreased rota-rod performance one week post-surgery but maintained the same spontaneous locomotor activity compared to the sham group [ 58 ], which may be related to development of more severe PTA in ACL transected mice than the mice receiving DMM surgery.…”