Untreated acute ankle sprains often result in chronic ankle instability (CAI) and can ultimately lead to the development of post-traumatic osteoarthritis (PTOA). At present, a typical animal model of ankle instability in mice is established by transecting the ligaments around the ankle joint. This study aimed to establish a grade I acute ankle sprain animal model by rapid stretching of peri-ankle joint ligaments. Furthermore, we tried to explore the pathophysiological mechanism of ankle osteoarthritis. In all, 18 male C57BL/6 J mice (7 weeks) were randomly divided into three groups: calcaneofibular ligament (CFL) laxity group, deltoid ligament (DL) laxity group, and SHAM group. One week after the surgical procedure, all mice were trained to run in the mouse rotation fatigue machine daily. The mice were tested on the balance beam before surgery and three days, 4 weeks, 8 weeks, and 12 weeks after surgery. Footprint analyses were performed on each mouse before surgery and 12 weeks after surgery. Micro-CT scanning was then performed to evaluate the degeneration of ankle joints and histological staining was performed to analyze and evaluate PTOA caused by ankle joint instability. After surgery, the mice in the CFL and DL laxity groups took longer to cross the balance beam and slipped more often than those in the SHAM group (p < 0.05). The step length and width in the CFL and DL laxity groups were significantly shorter and smaller than those in the SHAM group 12 weeks after surgery (p < 0.05). There was a significant increase in the bone volume fraction (BV/TV) in the CFL and DL laxity groups compared with the SHAM group (p < 0.05). Histological staining results suggested obvious signs of PTOA in the CFL and DL laxity groups. Based on CFL and DL laxity in a mouse ankle instability model, this study suggests that grade I ankle sprain can contribute to chronic ankle instability, impair motor coordination and balance, and eventually lead to PTOA of ankle with significant degeneration of its adjacent joints.

中文翻译：

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踝关节Ⅰ度扭伤后慢性踝关节不稳定对创伤后骨关节炎的影响


未经治疗的急性踝关节扭伤通常会导致慢性踝关节不稳定（CAI），并最终导致创伤后骨关节炎（PTOA）的发展。目前，典型的小鼠踝关节不稳定动物模型是通过横断踝关节周围韧带建立的。本研究旨在通过快速拉伸踝关节韧带建立I级急性踝关节扭伤动物模型。此外，我们试图探讨踝骨关节炎的病理生理机制。将18只雄性C57BL/6 J小鼠（7周）随机分为三组：跟腓韧带（CFL）松弛组、三角韧带（DL）松弛组和SHAM组。手术后一周，所有小鼠均接受每天在小鼠旋转疲劳机中跑步的训练。手术前和手术后三天、四周、八周和十二周对小鼠进行平衡木测试。在手术前和手术后 12 周对每只小鼠进行足迹分析。然后进行显微CT扫描评估踝关节退变情况，并进行组织学染色分析评估踝关节不稳定引起的PTOA。手术后，CFL 和 DL 松弛组的小鼠比 SHAM 组的小鼠需要更长的时间才能穿过平衡木，并且更容易滑倒 (p < 0.05)。术后 12 周，CFL 和 DL 松弛组的步长和宽度明显短于 SHAM 组 (p < 0.05)。与 SHAM 组相比，CFL 和 DL 松弛组的骨体积分数 (BV/TV) 显着增加 (p < 0.05)。组织学染色结果显示CFL​​和DL松弛组有明显的PTOA迹象。 基于小鼠踝关节不稳定模型中的 CFL 和 DL 松弛度，本研究表明，I 级踝关节扭伤可导致慢性踝关节不稳定，损害运动协调和平衡，并最终导致踝关节 PTOA 及其邻近关节的显着退化。