1. Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.
- Author
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Lin YY, Jbeily EH, Tjandra PM, Pride MC, Lopez-Torres M, Elmankabadi SB, Delman CM, Biris KK, Bang H, Silverman JL, Lee CA, and Christiansen BA
- Subjects
- Animals, Mice, Cartilage, Articular pathology, X-Ray Microtomography, Disease Models, Animal, Mice, Inbred C57BL, Male, Synovitis etiology, Synovitis surgery, Osteophyte etiology, Anterior Cruciate Ligament Injuries surgery, Anterior Cruciate Ligament Injuries complications, Osteoarthritis, Knee etiology, Osteoarthritis, Knee surgery, Osteoarthritis, Knee physiopathology, Disease Progression, Anterior Cruciate Ligament Reconstruction methods
- Abstract
Objective: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression., Design: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation., Results: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001)., Conclusions: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability., Competing Interests: Declaration of Competing Interest No author in this paper has competing interests to disclose., (Copyright © 2024 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2024
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