Osteoarthritis Research Unit, Université de Montréal Hospital Centre, Notre-Dame Hospital, 1560 Sherbrooke St. East, Montreal, QC, Canada H2L 4M1 ; GREPAQ, Department of Veterinary Biomedical Sciences, Faculty of Veterinary Medicine (FVM), Université de Montréal, P.O. Box 5000, Saint-Hyacinthe, QC, Canada J2S 7C6.
Biomed Res Int. 2013;2013:180453. doi: 10.1155/2013/180453. Epub 2013 Oct 31.
For many years Canis familiaris, the domestic dog, has drawn particular interest as a model of osteoarthritis (OA). Here, we optimized the dog model of experimental OA induced by cranial cruciate ligament sectioning. The usefulness of noninvasive complementary outcome measures, such as gait analysis for the limb function and magnetic resonance imaging for structural changes, was demonstrated in this model. Relationships were established between the functional impairment and the severity of structural changes including the measurement of cartilage thinning. In the dog model of naturally occurring OA, excellent test-retest reliability was denoted for the measurement of the limb function. A criterion to identify clinically meaningful responders to therapy was determined for privately owned dogs undergoing clinical trials. In addition, the recording of accelerometer-based duration of locomotor activity showed strong and complementary agreement with the biomechanical limb function. The translation potential of these models to the human OA condition is underlined. A preclinical testing protocol which combines the dog model of experimental OA induced by cranial cruciate ligament transection and the Dog model of naturally occurring OA offers the opportunity to further investigate the structural and functional benefits of disease-modifying strategies. Ultimately, a better prediction of outcomes for human clinical trials would be brought.
多年来,犬,即家犬,因其是骨关节炎(OA)模型而受到特别关注。在这里,我们优化了通过前十字韧带切断术诱导的实验性 OA 的犬模型。该模型证明了非侵入性补充结果测量(如步态分析以评估肢体功能和磁共振成像以评估结构变化)的有用性。在犬自然发生的 OA 模型中,肢体功能的测量表现出极好的测试-重测可靠性。为了确定接受临床试验的私人拥有的犬对治疗的临床有意义的反应标准,已经确定了一个标准。此外,基于加速度计的运动活动持续时间的记录与生物力学肢体功能具有很强的互补一致性。这些模型对人类 OA 状况的转化潜力得到了强调。将前十字韧带切断术诱导的实验性 OA 犬模型与犬自然发生的 OA 模型相结合的临床前测试方案为进一步研究疾病修饰策略的结构和功能益处提供了机会。最终,将更好地预测人类临床试验的结果。