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Satellite cells regulate the skeletal muscle environment by inhibiting fibroblast function
Author(s) -
Fry Christopher S,
Lee Jonah D,
Jackson Janna R,
Kirby Tyler J,
DupontVersteegden Esther E,
McCarthy John J,
Peterson Charlotte A
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1152.4
Subject(s) - extracellular matrix , muscle hypertrophy , paracrine signalling , fibroblast , myocyte , microbiology and biotechnology , fibronectin , skeletal muscle , fibrosis , satellite , medicine , biology , endocrinology , chemistry , cell culture , receptor , genetics , aerospace engineering , engineering
Interaction between satellite cells and the skeletal muscle extracellular matrix (ECM) has been demonstrated, but a role for satellite cells in regulating the ECM during hypertrophy has not been defined. We utilized mouse primary myoblasts and fibroblasts in co‐culture in addition to a genetically modified mouse model (Pax7‐DTA) to investigate the role of satellite cells in the regulation of muscle ECM. The Pax7‐DTA mouse allows for the conditional depletion of satellite cells in adult muscle following tamoxifen administration. Vehicle/tamoxifen treated animals were randomized to sham or synergist ablation surgery, leading to overload of the plantaris muscle for 1 and 8 weeks. Microarray analysis after 1 week of surgery showed the loss of satellite cells was associated with increased expression of numerous collagens and ECM structural genes. Depletion of satellite cells also led to attenuated hypertrophy and fibrosis of the plantaris with increases in both ECM deposition and fibroblast number following 8 weeks of overload. Co‐culturing mouse myoblasts with fibroblasts led to decreased mRNA expression of Col Ia2, IIIa1, VIa2 and Fibronectin compared to fibroblasts cocultured with fibroblasts, suggesting a paracrine role of myoblasts that inhibits fibroblast ECM production. We conclude that a novel function of satellite cells both at rest and during hypertrophy is to regulate muscle fibroblasts and the ECM. Funding: NIAMS R01AR060701, R21AG34453 and the Jeane B. Kempner Postdoctoral Award.