Skeletal muscle atrophy leads to loss and dysfunction of muscle precursor cells.
Atrophy of skeletal muscle leads to decreases in myofiber size and nuclear number; however, the effects of atrophic conditions on muscle precursor cells (MPC) are largely unknown. MPC lie outside myofibers and represent the main source of additional myonuclei necessary for muscle growth and repair. In the present study, we examined the properties of MPC after hindlimb suspension (HS)-induced atrophy and subsequent recovery of the mouse hindlimb muscles. We demonstrated that the number of MPC in atrophied muscles was decreased. RT-PCR analysis of cells isolated from atrophied muscles indicated that several mRNA characteristic of the myogenic program in MPC were absent. Cells isolated from atrophied muscles failed to properly proliferate and undergo differentiation into multinucleated myotubes. Thus atrophy led to a decrease in MPC and caused dysfunction in those MPC that remained. Upon regrowth of the atrophied muscles, these deleterious effects were reversed. Our data suggest that preventing loss or dysfunction of MPC may be a new pharmacological target during muscle atrophy.
Department of Pharmacology, Emory University School of Medicine, 5024 O. W. Rollins Research Center, Atlanta, GA 30322, USA.
Patrick O
PO
Mitchell
Grace K
GK
Pavlath
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D019417:Hindlimb Suspension; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000473:pathology* / Q000503:physiopathology*; D009133:Muscular Atrophy / Q000473:pathology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000032:analysis; D032496:Satellite Cells, Skeletal Muscle / Q000473:pathology; D013234:Stem Cells / Q000473:pathology*
D009124:Muscle Proteins; D012333:RNA, Messenger