Tendinosis-like histologic and molecular changes of the Achilles tendon to repetitive stress: a pilot study in rats

Clin Orthop Relat Res. 2011 Nov;469(11):3172-80. doi: 10.1007/s11999-011-2000-1. Epub 2011 Jul 29.


Background: Tendinopathy (pain and tendon degeneration) is associated with repetitive use and mechanical overload. However, the etiology of tendinopathy remains unclear. Clarification of histologic and molecular changes of tendon to repetitive stress could provide better understanding of Achilles tendon disorders related to repetitive stress.

Questions/purposes: We asked whether repetitive stress simulating overuse of the Achilles tendon induced (1) histologic changes in rats similar to tendinosis (increased cellularity of fibrocytes, increased disorganization of collagen fiber, and increased roundness of the nucleus of the fibrocyte), (2) increased collagen Type III occurrence, and (3) increased inducible nitric oxide synthase (iNOS) expression.

Methods: We used an exercise protocol simulating repetitive, jerky, eccentric contraction of the triceps surae in 15 rats. We conducted the exercise for 2 hours per day, three times per week using the right rear legs only and the left legs as internal controls. We harvested Achilles tendons after either 2, 4, or 6 weeks of exercise, and evaluated changes in tendon thickness, fibrocyte count, collagen fiber arrangement, collagen fiber type, and occurrence of iNOS.

Results: Exercised Achilles tendons showed increased cellularity of fibrocytes at 4 and 6 weeks of exercise, and disorganized collagen fiber arrangement at 6 weeks of exercise. There was a trend for Type III collagen occurrence being greater in experimental groups. Expression of iNOS increased after 2 and 4 weeks of exercise when compared with that of the controls, but decreased after 6 weeks.

Conclusions: These observations suggest repetitive, synchronized, passive, and jerky exercise induced by electrical stimulation can lead to the tendinosis-like changes in the Achilles tendons in rats with imbalance between synthesis and degeneration after 4 weeks of exercise.

Clinical relevance: This newly designed exercise protocol may be used to design an animal model of Achilles tendon overuse. With this model, therapeutic interventions of tendinopathy could be analyzed by investigation of tendon biology and response in terms of histologic and molecular changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / metabolism
  • Achilles Tendon / pathology*
  • Animals
  • Biomarkers / metabolism
  • Cell Nucleus / pathology
  • Collagen Type III / metabolism
  • Cumulative Trauma Disorders / metabolism
  • Cumulative Trauma Disorders / pathology*
  • Disease Models, Animal
  • Electric Stimulation
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Male
  • Muscle Contraction
  • Nitric Oxide Synthase Type II / biosynthesis
  • Physical Conditioning, Animal
  • Pilot Projects
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Mechanical
  • Tendinopathy / metabolism
  • Tendinopathy / pathology*


  • Biomarkers
  • Collagen Type III
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat