Epidemiological studies have shown that accumulated mechanical stress is a risk factor for the development of osteoarthritis (OA). This debilitating progressive clinical condition affects a broad spectrum of patients and will ultimately lead to definitive arthroplasty surgery as the endpoint treatment option in many cases. The aim of this study is to establish a graded murine model of OA by medial meniscotibial destabilisation of the knee joint and in phase two, to investigate the migration and engraftment of radioisotope labeled mesenchymal stem cells (MSCs) at varying points of disease progression. The first phase of the study was to establish the murine model, an Irish first. All procedures were performed aseptically under general anaesthesia via a midline medial parapatellar approach on a murine fracture table. Microsurgical dissection was performed through necropsy analysed layers to the joint space and the meniscotibial ligament identified and transected. Validated histopathological analysis was performed at two, four, eight and twelve weeks postoperatively. The results showed a gradation of OA changes from mild unicondylar changes at two weeks, moderate unicompartmental change at four, severe unicompartmental change at eight and severe bicompartmental change at twelve weeks post-operatively. In vivo Bazooka-Single Photon Emission Computed Tomography (SPECT) (Phase 2) imaging studies are currently ongoing following the model establishment.