Fast, non-eccentrically loaded exercise worsens tendinopathic healing responses in a murine model

Am J Vet Res. 2023 Apr 17;84(6):ajvr.23.01.0018. doi: 10.2460/ajvr.23.01.0018. Print 2023 Jun 1.

Abstract

Objective: To advance the understanding of how alterations in exercise speed and grade (flat vs 17° incline or decline) affect the quality of tendon healing, and to determine if a biomarker relationship exists between serum levels of a ColX breakdown product (CXM) and animals exposed to treadmill running protocols.

Animals: 35 male mice (C57BL/6J), 8 weeks of age.

Procedures: Mice were preconditioned on a treadmill for 14 days. Tendinopathy was then induced by 2 intra-tendinous TGFβ1 injections followed by randomization into 7 exercise groups. Exercise capacity and objective gait analysis were measured weekly. Mice were euthanized and histopathologic analysis and evaluation of serum CXM levels were performed. Statistics were conducted using a 2-way ANOVA (exercise capacity), Mixed Effects Model (gait analysis, effect of preconditioning), and 1-way ANOVA (gait analysis, the effect of injury, and rehabilitation normalized to baseline; CXM serum analysis), all with Tukey post hoc tests and significance set to P < .05.

Results: Exercise at a fast-flat speed demonstrated inferior tendinopathic healing at the cellular level and impaired stance braking abilities, which were compensated for by increased propulsion. Mice exposed to exercise (at any speed or grade) demonstrated higher systemic levels of CXM than those that were cage rested. However, no ColX immunostaining was observed in the Achilles tendon or calcaneal insertion.

Clinical relevance: Exercise at a fast speed and in absence of eccentric loading components (incline or decline) demonstrated inferior tendinopathic healing at the cellular level and impaired braking abilities that were compensated for by increased propulsion.

MeSH terms

  • Achilles Tendon* / metabolism
  • Achilles Tendon* / pathology
  • Animals
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Musculoskeletal Diseases* / pathology
  • Musculoskeletal Diseases* / veterinary
  • Tendinopathy* / therapy
  • Tendinopathy* / veterinary