title: Regulation of the muscle fiber microenvironment by activated satellite cells during hypertrophy.
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 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.
authors.affiliation: 1900 S. Limestone, CTW 105, University of Kentucky, Lexington, KY 40536, USA. cpete4@uky.edu.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Fry
authors.forename: Jonah D
authors.initials: JD
authors.lastname: Lee
authors.forename: Janna R
authors.initials: JR
authors.lastname: Jackson
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Kirby
authors.forename: Shawn A
authors.initials: SA
authors.lastname: Stasko
authors.forename: Honglu
authors.initials: H
authors.lastname: Liu
authors.forename: Esther E
authors.initials: EE
authors.lastname: Dupont-Versteegden
authors.forename: John J
authors.initials: JJ
authors.lastname: McCarthy
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D060833:Cellular Microenvironment; D016189:Dystrophin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006984:Hypertrophy; D007150:Immunohistochemistry; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics; D016474:Weight-Bearing
chemical_list: D016189:Dystrophin; D051763:PAX7 Transcription Factor; D013629:Tamoxifen; D018995:Myosin Heavy Chains
keywords: Pax7; Tcf4; extracellular matrix; fibroblast; myogenic progenitor cells