Characterizing a Novel and Adjustable Noninvasive Murine Joint Loading Model

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.