Novel in situ analysis of the functional impacts of osteoarthritis in the mouse model

About This Grant

Mouse models are an increasingly powerful tool in orthopaedic research, with continuous increases in the number and variety of popular methods for studying diseases such as osteoarthritis. While the use of these models is rapidly increasing, there has been little work in developing sophisticated techniques for assessing the biomechanical function of rodent joints, such as mouse knees. In this proposal, a novel force sensing universal robotic testing system will be applied to study multi-axial rodent joint biomechanics in both healthy and injured cases, allowing for clinically meaningful functional assessments of joint- and tissue-scale outcomes in powerful pre-clinical models. Specifically, the system will be used to study the immediate biomechanical effects of two common injury models: medial meniscus destabilization and anterior cruciate ligament rupture. Understanding the specific mechanical effects of these two injury models will improve experimental decision making, allowing for researchers to better select their models for future studies. Specifically, robotic testing will characterize changes in the relative motion of the knee under clinically relevant loads in both translational (anterior-posterior tibial drawers) and rotational (varus-valgus tibial rotation) loading paradigms, providing insight into the functional injury effects and potential signs of disease progression in multiple directions. The selection of physiologically relevant tests commonly performed in orthopaedic clinics will provide unique comparison points between mouse models of injury and osteoarthritis and published data from human subjects studies. Along with studies of the immediate functional effects of these injury models, in this proposal we describe a comparison of the structural and functional outcomes from three common models of orthopaedic trauma in the mouse. These models include the meniscus and ligament injuries described above, as well as a chronic overload model of cartilage damage. These three models will be implemented in animal cohorts and the overall effects of tissue structure, joint function, and individual tissue loading will be assessed. This information gained in this longer term study of three tissue damage models may be instrumental in identifying heightened injury risks in specific patient cohorts, and may lead to improved personalized medicine approaches through rehabilitation programming. Upon completion of this work, the novel robotic testing system may be applied to other joints from small animal models, including additional animals such as rats and rabbits, and additional joints such as elbows and shoulders. In summary, this work establishes a novel approach for quantifying changes in the biomechanical function of musculoskeletal joints in small animal injury models, with an initial application comparing the immediate and chronic impacts of three common models of osteoarthritis.