Articular cartilage degeneration following anterior cruciate ligament injury: a comparison of surgical transection and noninvasive rupture as preclinical.

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Presentation transcript:

Articular cartilage degeneration following anterior cruciate ligament injury: a comparison of surgical transection and noninvasive rupture as preclinical models of post-traumatic osteoarthritis T. Maerz, M.D. Newton, M.D. Kurdziel, P. Altman, K. Anderson, H.W.T. Matthew, K.C. Baker Osteoarthritis and Cartilage Volume 24, Issue 11, Pages 1918-1927 (November 2016) DOI: 10.1016/j.joca.2016.06.013 Copyright © 2016 Terms and Conditions

Fig. 1 Injury loading fixture and animal positioning to induce ACL rupture (A). Laxity was confirmed via an anterior drawer test (B, C). T = tibia; F = femur. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 2 Femoral and tibial AC thickness (A, B) and surface roughness (C, D) stratified by major compartments. An overall increase in AC thickness was observed in the femur and tibia of both injury groups at both time points. Surface Roughness was most elevated in the medial compartment of the femur in both injury groups whereas the trochlea did not exhibit significantly higher surface roughness at either time point (C). Transection exhibited significantly higher surface roughness in each tibial compartment compared to Rupture at both time points (D). Error bars represent the 95% confidence interval. *indicates significant difference to Control, P < 0.05. **indicates significant difference to Control, P < 0.001. ◊indicates significant difference between Rupture and Transection, P < 0.05. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 3 Femoral and Tibial AC Thickness (A, B) and Surface Roughness (C, D) stratified by subcompartment. At 4 weeks, differential AC thickness is observed in the subcompartments of the medial femur in both injury groups (A), and Transection exhibited significantly thicker AC in the lateral subcompartment of the medial femur at 10 weeks. On the tibia, the most drastic thickening was observed in the lateral subcompartment of the medial tibia (B). Surface roughness was highest in the medial femoral compartment in both injury groups (C), and little to no increases in surface roughness were observed on the trochlea. Transection exhibited significantly higher surface roughness compared to Rupture in all tibial subcompartments at 4 weeks (D). Error bars represent the 95% confidence interval. *indicates significant difference to Control, P < 0.05. **indicates significant difference to Control, P < 0.001. ◊indicates significant difference between Rupture and Transection, P < 0.05. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 4 Representative femoral AC height map. In Rupture and Transection, general cartilage thickening is evident in all compartments at both time points. A characteristic pattern of thickening and thinning is present in the medial condyle and, to a lesser extent, the lateral condyle. Zones of thinning subsided slightly in both injury groups at 10 weeks. L = lateral; M = medial. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 5 Representative tibial AC height maps. In Rupture and Transection, general cartilage thickening is evident at both time points, concentrated on the posterior aspect. Qualitatively, increased thickening can be seen on the lateral aspect of the medial plateau and the medial aspect of the lateral plateau. Transection exhibited a greater degree of posterior thickening and irregularity at both time points. A = anterior; M = medial; L = lateral. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 6 Comparison between contrast-enhanced μCT (A) and Safranin-O-stained histology (B) of the medial femoral condyle of a representative 4-week Rupture animal. The overall distribution of AC thickness as well as zones of both AC thickening (red arrows) and thinning (blue arrows) exhibit excellent agreement between the two analysis modalities. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 7 Representative Safranin-O-stained histologic sections of the medial and lateral femoral condyle of Control (A, B), Rupture (C, D), and Transection (E, F) at the 4 week time point. While Control cartilage is congruent with consistent thickness, native cellularity and zone-dependent cellular morphology, and even Saf-O staining distribution, both injury groups exhibit degenerative remodeling. On the medial femoral condyle, Rupture and Transection exhibit zones of hypercellular thickening (black arrows) and zones of hypocellular thinning (blue arrows) (C, E). Numerous superficial surface fissures were also noted (red arrows) (C, E). The lateral condyle of both injury groups exhibited overall thickening, abnormal cellular clonality (D, F), and some surface fissures (red arrows, D, F). Compared to Control, both Rupture and Transection exhibited significantly higher femoral histologic OARSI score at 4 and 10 weeks (G, H). *indicates significant difference to Control P < 0.05; **indicates significant difference to Control, P < 0.001. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions

Fig. 8 Representative Safranin-O-stained histologic sections of the medial and lateral tibial plateau of Control (A, B), Rupture (C, D), and Transection (E, F) at the 4 week time point. Control exhibits a smooth, congruent surface, even Saf-O distribution, and native cartilage thickening at the central weight-bearing aspect (A, B). Cartilage degeneration was evident in both Rupture and Transection, and superficial zones of hypocellular, Saf-O-devoid tissue are evident (red arrows, C, D, E, F). General cartilage thickening and surface irregularity are also observed in both groups. There was a significant increase in histologic OARSI score in both groups at both time points (G, H). *indicates significant difference to Control P < 0.05; **indicates significant difference to Control, P < 0.001. Osteoarthritis and Cartilage 2016 24, 1918-1927DOI: (10.1016/j.joca.2016.06.013) Copyright © 2016 Terms and Conditions