Alban Fouasson-Chailloux1,2,3,4, Marc Dauty1,2,3,4, Benoit Bodic1,4, Martial Masson1,5, Yves Maugars1,4,6, Benoit Metayer1,6, Joëlle Veziers1,5,7, Julie Lesoeur1,5, François Rannou8,9,10, Jérôme Guicheux1,4,7, Claire Vinatier1,4. 1. Inserm, UMR 1229, Regenerative Medicine and Skeleton, Université de Nantes, ONIRIS, Nantes, France. 2. Service de Médecine Physique et Réadaptation Locomotrice et Respiratoire, CHU Nantes, Nantes, France. 3. Service de Médecine du Sport, CHU Nantes, Nantes, France. 4. UFR Odontologie, Université de Nantes, Nantes, France. 5. CHU Nantes, Université de Nantes, Nantes, France. 6. Service de Rhumatologie, CHU Nantes, Nantes, France. 7. PHU4 OTONN, CHU Nantes, Nantes, France. 8. Service de Rééducation et de Réadaptation de l'Appareil Locomoteur et des Pathologies du Rachis, Hôpitaux Universitaires-Paris Centre, Groupe Hospitalier Cochin, Assistance Publique-Hôpitaux de Paris, Paris, France. 9. INSERM UMRS 1124, Toxicité Environnementale, Cibles Thérapeutiques, Signalisation Cellulaire et Biomarqueurs, UFR Sciences Fondamentales et Biomédicales, Paris, France. 10. Université de Paris, Paris, France.
Abstract
OBJECTIVES: Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis. METHODS: Twenty-four C57BL/6 male mice were randomly assigned to 3 groups (n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalkTM XT system until the 16th week after surgery. After animal sacrifices, histological and micro-computed tomographic assessment was performed. RESULTS: Operated knees showed a significant increase in the histological score compared with controls (P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus (P < 0.001) and on both sides after bilateral intervention (P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups (P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16. CONCLUSIONS: While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalkTM in the evaluation of mouse models of osteoarthritis.
OBJECTIVES: Osteoarthritis is a painful joint disease responsible for walking impairment. Its quantitative assessment by gait analysis in mice may be a relevant and noninvasive strategy to assess the disease severity. In this study, we aimed to determine the severity of osteoarthritis at the tissular and gait levels in unilateral and bilateral posttraumatic murine osteoarthritis. METHODS: Twenty-four C57BL/6 male mice were randomly assigned to 3 groups (n = 8/group): controls, unilateral surgery, and bilateral surgery. Posttraumatic osteoarthritis was induced unilaterally or bilaterally by destabilization of the medial meniscus. Gait analysis was performed weekly with the CatWalkTM XT system until the 16th week after surgery. After animal sacrifices, histological and micro-computed tomographic assessment was performed. RESULTS: Operated knees showed a significant increase in the histological score compared with controls (P < 0.001). Calcified anterior medial meniscal bone volume was higher on the ipsilateral side after unilateral destabilization of the medial meniscus (P < 0.001) and on both sides after bilateral intervention (P < 0.01). One week after surgery, the mice mean speed decreased significantly in both operated groups (P < 0.001 and P < 0.05). In the unilateral group, a significant increase in the contralateral hind print area appeared from week 4 to week 16. CONCLUSIONS: While bilateral destabilization of the medial meniscus induced no detectable gait modification except 1 week after surgery, unilateral model was responsible for a gait disturbance on the contralateral side. Further studies are needed to better define the place of the CatWalkTM in the evaluation of mouse models of osteoarthritis.
Entities:
Keywords:
destabilization of the medial meniscus; gait analysis; murine model; posttraumatic osteoarthritis
Authors: Ian J Wallace; Steven Worthington; David T Felson; Robert D Jurmain; Kimberly T Wren; Heli Maijanen; Robert J Woods; Daniel E Lieberman Journal: Proc Natl Acad Sci U S A Date: 2017-08-14 Impact factor: 11.205