Enomoto, S.; Arakawa, K.; Takahata, K.; Sato, M.; Miyamoto, H.; Saito, R.; Usami, Y.; Nogi, K.; Kokubun, T.

Objective: Recently, alternatives to animal testing, such as new approach methodologies, are being developed in the orthopedic research field; animal models still provide valuable insights into the pathogenesis of knee osteoarthritis (OA). However, commonly used models develop OA much more rapidly and severely than those observed in human patients. We aimed to develop a novel murine model that closely mimics the slow progression of human OA with posterior Cruciate ligament (PCL) rupture. Design: 12-week-old C57BL/6 mice were induced to PCL-rupture (PCL-R) by manually applying an external tibial posterior translation force. We analyzed joint kinematics, histological observations, and bone structure to confirm the absence of concurrent injury on day 0. Then, joint stability and the pathophysiological progression of knee OA were analyzed at 8, 16, and 34 weeks post-PCL-R. The destabilized medial meniscus (DMM) model was also analyzed to compare the OA progression. Results: Non-invasive PCL-R intervention induced the complete rupture in the central region of PCL without concurrent injury. The PCL-R group showed larger posterior tibial deviation than the INTACT (P=0.008). At 0day, the joint range of motion was not limited, but extension limitation occurred at 16 and 34weeks. Col-X positive-cell ratio in PCL-R was higher than INTACT (P=0.024) at 16weeks. Histologically, cartilage degeneration in PCL-R was milder than DMM. In the subchondral bone, trabecular thickness in DMM was higher than that in INTACT at 16 weeks (P=0.043). Trabecular number in PCL-R was higher than that in INTACT at 34 weeks (P=0.024). Conclusions: PCL-R model induced mild abnormal mechanical stress depending on posterior instability, and cartilage degeneration occurred more slowly in this model than in DMM animal models.