Surgical induction of posttraumatic osteoarthritis in the mouse

Given the prevalence and the scope of the personal and societal burden of OA, investigators have become increasingly interested in understanding the pathogenic basis of disease and developing novel disease-modifying OA therapies. Because of the well-documented central role that joint trauma plays in the initiation of knee OA, large animal and rodent models of knee injury that accurately recapitulate the OA disease process have become increasingly widespread over the past decade. To enable study in the context of defined genetic backgrounds, investigative teams have informally developed standardized protocols for injuring the mouse knee that aim to induce a reproducible degenerative process both in terms of severity and temporal pacing of disease progression. One such procedure, the meniscal/ligamentous injury (MLI) model of posttraumatic OA, is described in detail in this chapter. The description provided here sets the stage for both inexperienced and established investigators to employ the MLI procedure, or other similar surgical destabilization methods, to initiate the development of posttraumatic OA in the mouse. Successful application of this method provides a preclinical platform to study the mechanisms driving the pathogenesis of OA and to develop chondroprotective/regenerative strategies to treat it.