Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy

Christopher S Fry, Jonah D Lee, Janna R Jackson, Tyler J Kirby, Shawn A Stasko, Honglu Liu, Esther E Dupont-Versteegden, John J McCarthy, Charlotte A Peterson

Research output: Contribution to journalArticleAcademicpeer-review

203 Citations (Scopus)


Our aim in the current study was to determine the necessity of satellite cells for long-term muscle growth and maintenance. We utilized a transgenic Pax7-DTA mouse model, allowing for the conditional depletion of > 90% of satellite cells with tamoxifen treatment. Synergist ablation surgery, where removal of synergist muscles places functional overload on the plantaris, was used to stimulate robust hypertrophy. Following 8 wk of overload, satellite cell-depleted muscle demonstrated an accumulation of extracellular matrix (ECM) and fibroblast expansion that resulted in reduced specific force of the plantaris. Although the early growth response was normal, an attenuation of hypertrophy measured by both muscle wet weight and fiber cross-sectional area occurred in satellite cell-depleted muscle. Isolated primary myogenic progenitor cells (MPCs) negatively regulated fibroblast ECM mRNA expression in vitro, suggesting a novel role for activated satellite cells/MPCs in muscle adaptation. These results provide evidence that satellite cells regulate the muscle environment during growth.

Original languageEnglish
Pages (from-to)1654-65
Number of pages12
JournalFASEB Journal
Issue number4
Publication statusPublished - Apr 2014


  • Animals
  • Cell Proliferation
  • Cells, Cultured
  • Cellular Microenvironment
  • Dystrophin/metabolism
  • Extracellular Matrix/metabolism
  • Fibroblasts/cytology
  • Hypertrophy
  • Immunohistochemistry
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Fibers, Skeletal/drug effects
  • Muscle, Skeletal/metabolism
  • Myosin Heavy Chains/metabolism
  • Oligonucleotide Array Sequence Analysis
  • PAX7 Transcription Factor/genetics
  • Satellite Cells, Skeletal Muscle/cytology
  • Stress, Mechanical
  • Tamoxifen/pharmacology
  • Time Factors
  • Transcriptome/drug effects
  • Weight-Bearing

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