Characterization of a Novel Calcific Achilles Tendinopathy Model in Mice: Contralateral Tendinopathy Induced by Unilateral Tenotomy.

Abstract

Achilles tendinopathy is a significant clinical disease characterized by activity-related pain, focal movement limitation, and intratendinous imaging changes. However, treatment of Achilles tendinopathy has been based mainly on theoretical rationale and clinical experience because of its unclear underlying pathogenesis and mechanism. The purpose of the study was to develop a simple but reproducible overuse-induced animal model of Achilles tendinopathy in mice to better understand the underlying mechanism and prevent calcific Achilles tendinopathy. A total of 80 C57/B6 mice (8 or 9 weeks old) were employed and randomly divided into control and experimental groups. Unilateral Achilles tenotomy was performed on the right hind limbs in the experiment group. 12 weeks after unilateral Achilles tenotomy, the onset of Achilles tendinopathy in the contralateral Achilles tendon was determined by radiological assessment, histologic analysis, electron microscopy observation, and biomechanical test. The onset of calcific Achilles tendinopathy in contralateral Achilles tendon was confirmed after 12 weeks of unilateral tenotomy. The contralateral Achilles tendon in the experimental group was characterized as hypercellularity, neovascularization, and fused collagen fiber disarrangement, compared with the control group. Importantly, intra-tendon endochondral ossification and calcaneus deformity were featured in contralateral Achilles tendon. In addition, poor biomechanical properties in the contralateral Achilles tendon revealed the incidence of Achilles tendinopathy. We hereby introduce a novel, simple, but reproducible spontaneous contralateral calcific Achilles tendinopathy model in mice, which represents overuse conditions during tendinopathy development in humans. It should be a useful tool to further study the underlying pathogenesis of calcific Achilles tendinopathy.