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. 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. 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). 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.

中文翻译：

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手术重新稳定可减少小鼠 ACL 断裂引发的创伤后骨关节炎的进展


遭受前十字韧带 (ACL) 断裂等关节损伤的人通常会患上创伤后骨关节炎 (PTOA)。在人类患者中，ACL 损伤通常通过 ACL 重建来治疗。然而，目前尚不清楚关节再稳定对于减缓 PTOA 进展的效果如何。本研究的目的是确定非侵入性 ACL 损伤后小鼠膝关节的手术重新稳定如何影响 PTOA 进展。在这项研究中，187 只小鼠受到非侵入性 ACL 损伤或无损伤。受伤后，小鼠接受了重新稳定手术、假手术或不接受手术。然后在受伤/手术后第14天或第49天对小鼠实施安乐死。在多个时间点进行功能分析以评估随意运动、步态和疼痛。通过微型计算机断层扫描、RT-PCR 和全关节组织学对膝关节进行离体分析，以评估关节软骨退化、滑膜炎和骨赘形成。 ACL 损伤和手术均导致骨骺骨小梁丢失 (-27-32%)，并在早期时间点减少随意运动。关节重新稳定成功降低了 OA 评分（相对于第 14 天受伤的情况，−78%，p < 0.0001）和滑膜炎评分（相对于第 14 天受伤的情况，−37%，p = 0.042），并减少了软骨赘/骨赘的形成（相对于第 14 天受伤的情况为 -97%，p < 0.001，第 49 天受伤的情况为 -78%，p < 0.001）。这项研究证实，手术膝关节重新稳定可以有效减少小鼠 ACL 损伤后的关节软骨退化和软骨赘/骨赘形成，表明这些过程很大程度上是由该小鼠模型中的关节不稳定驱动的。 然而，重新稳定无法减轻早期炎症反应和骨骺小梁骨的丢失，表明这些过程与关节不稳定性无关。