Osteoarthritis (OA) is the most common cause of disability in the elderly [
1]. Disability stems from pain and limitations in mobility secondary to the degeneration of articular cartilage, a trademark of the disease. Unfortunately, current pharmacological therapy targeting the mechanism of OA is relatively ineffective, largely because the etiology and pathogenesis of OA remain poorly understood. The complex pathobiological changes that occur in human OA may be influenced by a multitude of genetic and environmental factors. The effort to clarify the molecular events that occur in OA during the onset and the progression of OA has necessitated the use of in vivo models [
2]. Researchers tend to utilize knee OA models to investigate these factors, but have neglected the establishment of other types of OA models, such as ankle OA.
A recent study indicates that the biomarker and mechanism of ankle OA may not be the same as those of knee OA [
3‐
5]. Researchers have reported that aggrecan (Acan), bone morphogenetic protein (BMP)-2, BMP-7, and fibronectin-aggrecan complex (FAC) can be used as key markers of OA in the ankle, but not in the knee [
6,
7]. In the knee and hip, primary OA accounts for 67% and 58% of all cases, respectively. Meanwhile, 78% of all cases of ankle OA are post-traumatic (PTOA) [
8,
9]. In addition, while the incidence of knee OA in the adult population rises from 6% to 10% after 65 years of age, the incidence of ankle OA remains unchanged with age [
10]. Malleolar fractures are the most frequent type of fracture in the ankle, presenting in 37–53% of patients with advanced or end-stage ankle OA [
11,
12]. More than 50% of patients with fractures of the distal tibial articular surface develop OA [
13]. After intra-articular fracture, the ankle joint sustains increased contact stress; in addition, the inflammatory response is a contributory factor to the progress of OA [
14]. Chondrocyte necrosis and apoptosis are observed following trauma in human and porcine knees, and associated with cartilage damage and degeneration [
15]. An advantage of PTOA models is that there is temporal control of disease induction (when compared with spontaneous animal OA and with human disease), while mimicking the molecular pathology and histopathology of human disease [
2]. Despite the high incidence of ankle trauma and OA, ankle-specific OA research is sparse, with the majority of clinical and basic research pertaining to the knee and hip joints [
16]. This will greatly limit the study of ankle OA. Thus, there is a need to develop novel ankle PTOA models to facilitate research of this type of OA. Clinically, some patients with malleolar fracture present only, while others present with fracture and dislocation. Therefore, we developed two rat ankle PTOA models in this study: 1) the malleolus fracture with dislocation and reduction; and 2) the malleolus fracture alone. The contralateral ankles were used as controls. To validate the success of our models, X-ray and Safranin-O were used to observe morphological changes in the subchondral bone, joint space and cartilage. FMT, ELISA and immunohistochemistry were used to detect protein levels of several OA-related biomarkers, and qPCR was used to obtain the mRNA levels of several OA related genes.