A mouse model of ankle-subtalar joint complex instability induced post-traumatic osteoarthritis

Abstract

Background Ankle-subtalar joint complex instability is not uncommonly presented in the clinic, but symptoms and signs similar to other conditions can easily lead to its misdiagnosis. Due to the lack of appropriate animal models, research on ankle-subtalar joint complex instability is limited. The aims of the present study were to establish an animal model of ankle-subtalar joint complex instability in mice and to explore its relationship with post-traumatic osteoarthritis (PTOA). Methods Twenty-one male C57BL/6J mice were randomly divided into three groups: SHAM group (sham surgery group), transected cervical ligament + anterior talofibular ligament (CL+ATFL) group, and transected cervical ligament + deltoid ligament (CL+DL) group. Two weeks after surgery, all mice underwent cage running training. Balance beam and gait tests were used to evaluate the changes in self-movement in the mice after ankle-subtalar ligament injury. Micro-CT and histological staining were used to evaluate the progress of PTOA. Results Compared with the SHAM group, balance and gait were affected in the ligament transection group. Twelve weeks after surgery, the time required to cross the balance beam in the CL+ATFL group was 35.1% longer and the mice slipped 3.6-fold more often than before surgery, and the mean step length on the right side was 7.2% smaller than that in the SHAM group. The time required to cross the balance beam in the CL+DL group was 32.1% longer and the mice slipped 3-fold more often than prior to surgery, and the average step length on the right side was 5.6% smaller than that in the SHAM group. CT images indicated that 28.6% of the mice in the CL+DL group displayed dislocation of the talus. Tissue staining suggested that articular cartilage degeneration occurred in mice with ligament transection 12 weeks after surgery. Conclusions Transected mice in the CL+ATFL and CL+DL groups displayed mechanical instability of the ankle-subtalar joint complex, and some mice in the CL+DL group also suffered from talus dislocation due to ligament injury leading to loss of stability of the bone structure. In addition, as time progressed, the articular cartilage displayed degenerative changes, which affected the ability of animals to move normally.

Exosomes derived from platelet-rich plasma administration in site mediate cartilage protection in subtalar osteoarthritis

“…It was confirmed that the lateral ligamentectomy of ATFL and CFL only induced the occurrence of subtalar OA, and had almost no effect on talocrural joint. In 2021, Liu et al [ 76 ] believed that the resection of the lateral ligaments would not only cause the degeneration of subtalar joint, but also affect the development of the medial talocrural OA. Although there is some controversy over whether the lateral ligament resection model can induce the degeneration of talocrural joint, it is certain that the lateral ligament resection can provide a reliable animal model of STOA.…”

A new mouse model of ankle instability induced by multiple mechanical sprains with controlled inversion angle and speed

“…Depending on different populations, up to 70% of patients suffering from lateral ankle sprain develop CAI (Fong et al, 2007;Swenson et al, 2009;Hiller et al, 2012). CAI has also been found to have a higher risk of developing posttraumatic osteoarthritis (Gribble et al, 2016;Liu et al, 2021;Li et al, 2022).…”

“…Currently, two ankle sprain models have been developed. The first one is a mouse model by surgically transecting the CFL and ATFL (Kim et al, 2008;Kim et al, 2011;Hubbard-Turner et al, 2013;Wikstrom et al, 2015;Liu et al, 2021;Li et al, 2022). The second one is a rat model induced by manually overextending the ankle repeatedly in the plantarflexion and inversion directions (Koo et al, 2002).…”

Sequelae of subtalar joint dislocations at two level 1 trauma centers: A case series and literature review

“…[1][2] Subtalar joint dislocations are defined by dislocations of the talocalcaneal and talonavicular joints without involvement of the ankle joint. [1][2][3] The etiology of these injuries are most commonly high energy trauma, such as motor vehicle accidents or falls from height. Low energy etiologies are less common, but they can occur with sports, ground level falls, or other eversion/inversion injuries of the foot.…”

“…Additionally, functional outcomes may be hampered by high rates of post-traumatic osteoarthritis (OA). [2][3][4] Due to the rarity of the pathology, cases of subtalar joint dislocations are not often reported. Hence, the question remains whether modern complication rates are as great as those reported historically.…”