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 journalArticlepeer-review

    143 Scopus citations

    Abstract

    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 celldepleted 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 (US)
    Pages (from-to)1654-1665
    Number of pages12
    JournalFASEB Journal
    Volume28
    Issue number4
    DOIs
    StatePublished - Apr 2014

    Keywords

    • Extracellular matrix
    • Fibroblast
    • Myogenic progenitor cells
    • Pax7
    • Tcf4

    ASJC Scopus subject areas

    • Biotechnology
    • Biochemistry
    • Molecular Biology
    • Genetics

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