Characterizing a novel and adjustable noninvasive murine joint loading model

Abstract

Objective. Mechanical loading through a mechano-adaptive response modifies articular cartilage structure and contributes to osteoarthritis (OA). However, the specific mechanical stimuli involved in joint health and disease remain poorly defined, partly due to a lack of in vivo models of controlled loading. The present study was undertaken to develop and characterize a novel nonsurgical murine model in which applied loads to the knee joint are highly adjustable.Methods. Animals experienced normal locomotion, except during loading. Loads were applied to the right knees of 8-week-old CBA mice, 3 times a week for 2 weeks (and assessed immediately or after 3 weeks of nonloading), or for 5 weeks, or just once (and assessed immediately or after 2 weeks of nonloading). Histologic features of loaded and control contralateral joints, including articular cartilage lesions, osteophyte formation, and pathologic features, were examined. Ex vivo visualization during loading was performed by microfocal computed tomography (micro-CT).Results. Two weeks of loading produced articular cartilage lesions only at sites of maximal contact as exhibited by micro-CT; after 3 weeks without further loading, joints in another group of mice identically loaded revealed significant increases in mean lesion severity to levels seen following 5 weeks of loading. Single application of load also induced lesions, but in this case, 2 weeks of solely habitual use did not lead to further deterioration. Only repetitive loading induced loss of Safranin O staining. Loading also led to osteophyte formation, meniscal ossification, synovial hyperplasia and fibrosis, and cruciate ligament pathology, with a severity that was dependent upon the loading regimen utilized.Conclusion. We describe for the first time a noninvasive model of murine knee joint loading. This will further the study of mechanical and genetic interactions in joint health and in OA initiation and progression.

Role of subchondral bone properties and changes in development of load-induced osteoarthritis in mice

“…Using a peak load of 9N for 1200 cycles, this model induced controlled instabilities in the knee joint 31 , and recapitulated OA pathology in the cartilage and SCB after 1, 2, and 6 weeks of daily loading in adult C57BL/6 mice 27,28 . A single bout of loading also induced disease initiation and progression, demonstrating that OA pathology in this model can be initiated by cell-mediated processes that are activated by mechanical loading 32 .…”

“…We and others have recently developed a non-invasive load-induced model of OA in the mouse 27,28 , based on controlled cyclic compression of the tibia and initially intended for bone adaptation studies 29,30 . Using a peak load of 9N for 1200 cycles, this model induced controlled instabilities in the knee joint 31 , and recapitulated OA pathology in the cartilage and SCB after 1, 2, and 6 weeks of daily loading in adult C57BL/6 mice 27,28 .…”

Cartilage tissue engineering

“…Furthermore, implantation of chondrocyte subpopulations in depth-dependent defects as well as separate seeding strategies was possible. A recent non-invasive model has been described which loads a murine joint [114] . In this case, after 2 weeks of intermittent loading regimens, the authors reported signifi cant differences in lesion severity dependent on loading period intensity and time of analysis post-loading.…”

Untitled

“…Load cycles consisted in a 0.1 s trapezoidal load, in which peak loads of 13 N were applied for 0.05 s, with loading and unloading times of 0.025 s, separated by a 9.9 s baseline rest period (De Souza et al, 2005;Poulet et al, 2011). These were applied at 40 cycles/day, three times a week for 2 weeks.…”

“…Loading conditions were determined from a study by Poulet et al (2011), where μCT imaging was employed to visualise the knee joint during axial loading.…”