Title | Effective fiber hypertrophy in satellite cell-depleted skeletal muscle. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | McCarthy JJ, Mula J, Miyazaki M, Erfani R, Garrison K, Farooqui AB, Srikuea R, Lawson BA, Grimes B, Keller C, Van Zant G, Campbell KS, Esser KA, Dupont-Versteegden EE, Peterson CA |
Journal | Development |
Volume | 138 |
Issue | 17 |
Pagination | 3657-66 |
Date Published | 2011 Sep |
ISSN | 1477-9129 |
Keywords | Animals, Blotting, Western, Female, Flow Cytometry, Hypertrophy, Mice, Muscle Fibers, Skeletal, Muscle, Skeletal, Polymerase Chain Reaction, Satellite Cells, Skeletal Muscle, Tamoxifen |
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. |
DOI | 10.1242/dev.068858 |
Alternate Journal | Development |
PubMed ID | 21828094 |
PubMed Central ID | PMC3152923 |
Grant List | R21 AG034453 / AG / NIA NIH HHS / United States R01 AR045617 / AR / NIAMS NIH HHS / United States R01 HL090749 / HL / NHLBI NIH HHS / United States AG020941 / AG / NIA NIH HHS / United States R01 AG020941 / AG / NIA NIH HHS / United States AR060701 / AR / NIAMS NIH HHS / United States R01 AR060701 / AR / NIAMS NIH HHS / United States AG034453 / AG / NIA NIH HHS / United States HL090749 / HL / NHLBI NIH HHS / United States AR045617 / AR / NIAMS NIH HHS / United States |