Destabilisation of the medial meniscus: imaging and mechanics of a murine surgical osteoarthritis model

Abstract

Destabilisation of the medial meniscus (DMM) is a murine surgical instability model of osteoarthritis (OA). In this thesis the bone and cartilage changes were examined at different time points and in different strains of mice in the DMM model. In the first study C57Bl/6 mice underwent DMM surgery and were culled four and eight weeks postoperatively. Tibiae were examined using confocal scanning laser microscopy (CSLM) for cartilage changes and micro-computed tomography (micro-CT) for bone changes. Additional mice underwent laxity testing. The tibia exhibited significant loss of cartilage and bone on the posterior plateau. A significant increase of anterior-posterior laxity suggested that damage of the anterior cruciate ligament had occurred during surgery, which permitted the femur to relocate to posterior tibia causing bone and cartilage damage. A second study investigated early stage bone changes in the DMM model. CSLM and micro-CT were used in conjunction with non-decalcified histology. Mice received calcein injections three and six days prior to sacrifice, and were culled two weeks after surgery. There was an increase of epiphyseal bone volume. No change in cartilage was observed with CSLM. A significant increase of mineralising surface/bone surface and osteoid surface/bone surface occurred at two weeks. A final study compared the bone response of two mice strains (BALB/c and C57Bl/6). Laxity was compared between strains eight weeks post operatively. Epiphyseal bone increased in both strains, more so in the BALB/c which had initially less epiphyseal bone volume. There was no change in histological mineralisation parameters or laxity measures. In this work multi-modal imaging techniques were developed to determine the change in bone and cartilage in the DMM model.