Abstract
INTRODUCTION
Loss of joint function is only exploited in osteoarthritis (OA) once severe impairment is apparent. Animal models allow for lesion induction and serial OA progression measures. We recently described an adjustable non-surgical loading model for generating focal cartilage lesions in only the lateral femur joint compartment, in which regimes can be adjusted so that these either do or do not progress spontaneously. Herein, we use ventral plane videographic treadmill gait analysis to determine whether gait changes can be used to discriminate between stable and spontaneously progressing lesions, induced by these two loading regimes.
METHODS
Animals encountered normal conditions, except during loading (9N, 40 cycles, 0.1 Hz, 10 sec/ cycle) which was applied to right knees in two groups (n=8) of 8-week-old male CBA mice: i) loaded once; ii) loaded 3 times/week for 2 weeks. Gait (including: brake, propel, stance, stride, stride length, stride frequency, steps and paw area) was assessed 3 times/week for 2 weeks in each mouse using a DigigaitTM treadmill. Thereafter, mice received 5mg/kg carprofen for analgesia and gait analysis repeated on 3 further alternate days.
RESULTS
The two loading regimes produced virtually identical gait modifications with delayed onset (apparent on day 3) which remained unchanged for 2 weeks; mice loaded once only showed modified contralateral limb use, but those loaded multiply exhibited additional ipsilateral front limb modifications; no changes in gait were observed in loaded limbs. Intriguingly, the two regimes produced distinct responses to analgesia. Load-induced gait changes were completely rescued by carprofen in mice loaded only once, whilst those in mice loaded repetitively persisted.
CONCLUSION
Our findings reveal specific and reproducible, compensatory changes in contralateral, non-loaded limb gait induced by any joint loading which produces focal articular lesions, and modified ipsilateral front limb use only when progressing lesions are induced by repetitive loading. We find that pain relief completely alleviates all gait modifications associated with stable lesions induced by single loading, but not those induced by repetitive loading. Differing responses in mice with stable and progressive articular cartilage load-induced lesions suggests that gait behaviour in a mechanical loading model of OA may predict joint degeneration.
