Graded ankle instability induces early osteoarthritic changes in a rat model

To use a rat model of graded ankle instability and mechanical laxity observed in ankle sprains to examine early cartilage degeneration and explore molecular alterations.

Graded ankle instability was induced by transection of the anterior talofibular and calcaneofibular ligaments, resulting in the following experimental groups: sham-operated control group; transected calcaneofibular ligament group; and combined transected anterior talofibular and calcaneofibular ligament group. Radiographic and histological analyses were performed at 4, 6, and 8 weeks postoperatively, and functional performance was assessed using the ladder walking test. Moreover, an exploratory RNA sequencing analysis of ankle cartilage was conducted to identify differentially expressed genes (DEGs) in early osteoarthritic and normal cartilage. Gene Ontology and network analyses were conducted using a Gene Set Enrichment Analysis.

The anterior drawer distance and talar tilt angle increased proportionally with ligament transection, thus confirming graded mechanical instability. The histological evaluation showed severity-dependent cartilage degeneration with increased Osteoarthritis Research Society International scores associated with the degree of instability. Exploratory RNA sequencing identified 245 significant DEGs (132 upregulated and 113 downregulated) with macrophage-related gene enrichment. Among these, CCL2 and TRPV4 with osteoarthritis progression were highlighted as existing genes that potentially link mechanical stress to inflammatory responses in cartilage.

This graded ankle instability model allowed an experimental evaluation of relationships between joint instability, early cartilage degeneration, and associated molecular changes.