Changes in macrophage phenotype and induction of epithelial-to-mesenchymal transition genes following acute Achilles tenotomy and repair

J Orthop Res. 2014 Jul;32(7):944-51. doi: 10.1002/jor.22624. Epub 2014 Apr 4.


Tendon injuries occur frequently in physically active individuals, but the clinical outcomes for these injuries can be poor. In many injured tissues the repair process is orchestrated by two types of cells, macrophages and fibroblasts. Macrophages, which have both pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, can directly participate in tissue remodeling and direct the response of other cells through the secretion of cytokines and growth factors. In many organ systems, epithelial cells can trans-differentiate into fibroblasts, which can then regenerate damaged ECM. This process is triggered via activation of epithelial-to-mesenchymal transition (EMT) signaling programs. Most tendons are surrounded by sheets of epithelial cells, and these tissue layers could provide a source of fibroblasts to repair injured tendons. To gain greater insight into the biology of tendon repair, we performed a tenotomy and repair in Achilles tendons of adult rats and determined changes in macrophage phenotype, and ECM- and EMT-related genes over a 4-week time course. The results from this study suggest that changes in macrophage phenotype and activation of EMT-related programs likely contribute to the degradation and subsequent repair of injured tendon tissue.

Keywords: epithelial-to-mesenchymal transition; fibrosis; macrophage; repair; tendon.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Achilles Tendon / injuries*
  • Achilles Tendon / pathology
  • Achilles Tendon / surgery*
  • Animals
  • Cell Differentiation
  • Epithelial-Mesenchymal Transition*
  • Fibroblasts / metabolism
  • Fibrosis
  • Gene Expression Regulation
  • Inflammation
  • Macrophages / cytology*
  • Macrophages / metabolism
  • Male
  • Phenotype
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tendon Injuries / surgery*
  • Tenotomy*
  • Time Factors
  • Wound Healing / physiology*