Histology of the naïve control and OA knee joints. A, C, knee from a naive animal has normal cartilage (arrows). Higher magnification of medial compartment from naive animal shows normal cartilage (arrows). B, D, knee from one month OA animal has significant cartilage degeneration on all articulating surfaces, with the greatest lesion severity on the medial femur (large arrows). There is severe atrophy of the medial tibia, as well as marked a reshaping of the medial tibial plateau and tibial epiphyseal bone. Additionally, there is a medium-sized osteophyte on the medial femur (small arrow). There is severe thickening/fibrous repair with proteoglycan on the medial side of the synovium and joint capsule. M = Medial; L = Lateral; S = Synovium; m = Meniscus; C = Cruciate ligaments. E, total joint score in OA knees (12.17 ± 0.9, N = 10) were significantly higher than in naïve control knees (0.47 ± 0.23; N = 7; P < 0.001; Mann-Whitney U-test). F, Medial cartilage degeneration was more severe than that of the lateral cartilage (4.53 ± 0.49, N = 10 vs. 2.4 ± 0.53, N = 10, respectively; P = 0.008; Student's t-test). Moreover, tibia cartilage degeneration was more severe than femur cartilage degeneration (4.53 ± 0.49, N = 10 vs. 2.4 ± 0.53, N = 10, respectively; P = 0.003; Student's t-test).