Resident stem cells are not required for exercise-induced fiber-type switching and angiogenesis but are necessary for activity-dependent muscle growth.
Skeletal muscle undergoes active remodeling in response to endurance exercise training, and the underlying mechanisms of this remodeling remain to be defined fully. We have recently obtained evidence that voluntary running induces cell cycle gene expression and cell proliferation in mouse plantaris muscles that undergo fast-to-slow fiber-type switching and angiogenesis after long-term exercise. To ascertain the functional role of cell proliferation in skeletal muscle adaptation, we performed in vivo 5-bromo-2'-deoxyuridine (BrdU) pulse labeling (a single intraperitoneal injection), which demonstrated a phasic increase (5- to 10-fold) in BrdU-positive cells in plantaris muscle between days 3 and 14 during 4 wk of voluntary running. Daily intraperitoneal injection of BrdU for 4 wk labeled 2.0% and 15.4% of the nuclei in plantaris muscle in sedentary and trained mice, respectively, and revealed the myogenic and angiogenic fates of the majority of proliferative cells. Ablation of resident stem cell activity by X-ray irradiation did not prevent voluntary running-induced increases of type IIa myofibers and CD31-positive endothelial cells but completely blocked the increase in muscle mass. These findings suggest that resident stem cell proliferation is not required for exercise-induced type IIb-to-IIa fiber-type switching and angiogenesis but is required for activity-dependent muscle growth. The origin of the angiogenic cells in this physiological exercise model remains to be determined.
Li
Ping
P
Department of Medicine, Duke University Medical Center, Independence Park Facility, 4321 Medical Park Dr., Durham, NC 27704, USA.
Akimoto
Takayuki
T
Zhang
Mei
M
Williams
R Sanders
RS
Yan
Zhen
Z
D000222:Adaptation, Physiological / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression; D015151:Immunoblotting; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018656:Muscle Fibers, Fast-Twitch / Q000166:cytology / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic; D009687:Nuclear Proteins / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
C502132:CDC6 protein, mouse; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins