title: Effective fiber hypertrophy in satellite cell-depleted skeletal muscle.
abstract: An important unresolved question in skeletal muscle plasticity is whether satellite cells are necessary for muscle fiber hypertrophy. To address this issue, a novel mouse strain (Pax7-DTA) was created which enabled the conditional ablation of >90% of satellite cells in mature skeletal muscle following tamoxifen administration. To test the hypothesis that satellite cells are necessary for skeletal muscle hypertrophy, the plantaris muscle of adult Pax7-DTA mice was subjected to mechanical overload by surgical removal of the synergist muscle. Following two weeks of overload, satellite cell-depleted muscle showed the same increases in muscle mass (approximately twofold) and fiber cross-sectional area with hypertrophy as observed in the vehicle-treated group. The typical increase in myonuclei with hypertrophy was absent in satellite cell-depleted fibers, resulting in expansion of the myonuclear domain. Consistent with lack of nuclear addition to enlarged fibers, long-term BrdU labeling showed a significant reduction in the number of BrdU-positive myonuclei in satellite cell-depleted muscle compared with vehicle-treated muscle. Single fiber functional analyses showed no difference in specific force, Ca(2+) sensitivity, rate of cross-bridge cycling and cooperativity between hypertrophied fibers from vehicle and tamoxifen-treated groups. Although a small component of the hypertrophic response, both fiber hyperplasia and regeneration were significantly blunted following satellite cell depletion, indicating a distinct requirement for satellite cells during these processes. These results provide convincing evidence that skeletal muscle fibers are capable of mounting a robust hypertrophic response to mechanical overload that is not dependent on satellite cells.
authors.affiliation: Department of Physiology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: McCarthy
authors.forename: Jyothi
authors.initials: J
authors.lastname: Mula
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Rod
authors.initials: R
authors.lastname: Erfani
authors.forename: Kelcye
authors.initials: K
authors.lastname: Garrison
authors.forename: Amreen B
authors.initials: AB
authors.lastname: Farooqui
authors.forename: Ratchakrit
authors.initials: R
authors.lastname: Srikuea
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Lawson
authors.forename: Barry
authors.initials: B
authors.lastname: Grimes
authors.forename: Charles
authors.initials: C
authors.lastname: Keller
authors.forename: Gary
authors.initials: G
authors.lastname: Van Zant
authors.forename: Kenneth S
authors.initials: KS
authors.lastname: Campbell
authors.forename: Karyn A
authors.initials: KA
authors.lastname: Esser
authors.forename: Esther E
authors.initials: EE
authors.lastname: Dupont-Versteegden
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Peterson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D006984:Hypertrophy / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D013629:Tamoxifen