Characterising anterior cruciate ligament injury in a non-surgical model of post-traumatic osteoarthritis. — The Association Specialists
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Characterising anterior cruciate ligament injury in a non-surgical model of post-traumatic osteoarthritis. (315)

Carina Blaker 1 , Miriam T Jackson 2 , Christopher B Little 2 , Elizabeth Clarke 1
  1. Murray Maxwell Biomechanics Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia
  2. Raymond Purves Bone and Joint Research Laboratory, Kolling Institute of Medical Research, University of Sydney, Royal North Shore Hospital, St. Leonards, NSW, Australia

Joint trauma is a significant risk factor for the development of post-traumatic osteoarthritis (ptOA) but the molecular mechanisms driving disease initiation and progression remain unclear. Answering this requires use of models mimicking clinically relevant ptOA-inducing injuries, most commonly surgical meniscal or anterior cruciate ligament (ACL) injury. Surgical trauma itself limits the utility of these models to evaluate the importance of acute post-injury inflammation in long-term ptOA development. Therefore in the current study, a non-surgical ACL rupture model was characterised.
In cadaveric mice (9-52 week C57Bl-6), factors potentially influencing ACL failure (age, gender, body-mass) were assessed. A custom built loading apparatus was used to induce progressive posterior femoral translocation relative to the tibia at a loading rate of 1 mm/s. ACL failure was determined from deflection of force-displacement curves and verified by gross and histopathological evaluation; failure load and stiffness (slope of force-displacement curve) were determined.
Mixed model linear regression determined that mass was positively associated with rupture load (p<0.001) but age and gender had no significant effect when corrected for the other covariates. In contrast, stiffness was correlated with increasing age (p=0.033) and was significantly higher in females (p<0.001). All ACLs failed at the femoral attachment. Based on these observations, knees in anaesthetised 10-12 week, male C57Bl-6 mice were loaded to ACL failure or 55% of mean failure load. We confirmed that mass remained positively correlated to rupture load (p=0.008) but not stiffness (p=0.408) in live mice. There was no difference in stiffness or rupture load between live and cadaveric mice when corrected for mass (p=0.756, p=0.525).
We have developed a non-surgical model in mice where ACL loading and failure can be controlled. Ongoing studies will use this model to determine the inflammatory response in ptOA development that is uncomplicated by post-surgery inflammation, and the role of sub-failure ACL injury.