Joint instability causes catabolic enzyme production in chondrocytes prior to synovial cells in novel non-invasive ACL ruptured mouse model. Issue 5 (May 2023)

• Record Type: Journal Article
• Authors: Takahata, K.; Arakawa, K.; Enomoto, S.; Usami, Y.; Nogi, K.; Saitou, R.; Ozone, K.; Takahashi, H.; Yoneno, M.; Kokubun, T.
• Is Part Of: Osteoarthritis and cartilage. Volume 31:Issue 5(2023)
• Page Start: 576
• Page End: 587
• Publication Date: 2023-05
• Subjects: Osteoarthritis -- Animal model -- Mechanical stress -- Synovitis; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Osteoarthritis -- Periodicals; Cartilage -- Periodicals; Arthrose -- Périodiques; Articulations -- Maladies -- Périodiques; 616.7223005
• DOI: 10.1016/j.joca.2022.12.004
• Languages: English
• ISSNs: 1063-4584

Abstract

Summary: Objective: The Anterior Cruciate Ligament (ACL)-deficient model helps to clarify the mechanism of knee osteoarthritis (OA); however, the conventional ACL injury model could have included concurrent onset factors such as direct compression stress to cartilage and subchondral bone. In this study, we established a novel Non-invasive ACL-Ruptured mouse model without concurrent injuries and elucidated the relationship between OA progression and joint instability. Design: We induced the ACL-Rupture non-invasively in twelve-week-old C57BL/6 male mice and evaluated histological, macroscopical, and morphological analysis at 0 days. Next, we created the ACL-R, controlled abnormal tibial translation (CATT), and Sham groups. Then, the joint stability and OA pathophysiology were analyzed at 2, 4, and 8 weeks. Results: No intra-articular injuries, except for ACL rupture, were observed in the ACL-R model. ACL-R mice increased anterior tibial displacement compared to the Sham group ( P < 0.001, 95% CI [−1.509 to −0.966]) and CATT group ( P < 0.001, 95% CI [−0.841 to −0.298]) at 8 weeks. All mice in the ACL-R group caused cartilage degeneration. The degree of cartilage degeneration in the ACL-R group was higher than in the CATT group ( P = 0.006) at 8 weeks. The MMP-3-positive cell rate of chondrocytes increased in the ACL-R group than CATT group from 4 weeks ( P = 0.043; 95% CI [−28.32 to −0.364]) while that of synovial cells increased at 8 weeks ( P = 0.031; 95% CI [−23.398 to −1.021]). Conclusion: We successfully established a Non-invasive ACL-R model without intra-articular damage. Our model revealed that chondrocytes might react to abnormal mechanical stress prior to synovial cells while the knee OA onset.