Muscle regeneration in the prolonged absence of myostatin.
Myostatin is an endogenous inhibitor of muscle conserved across diverse species. In the absence of myostatin, there is massive muscle growth in mice, cattle, and humans. Previous studies in the mdx mouse model of muscular dystrophy demonstrate that inhibiting myostatin attenuates several features of dystrophic muscle. These findings have encouraged the development of human therapies to block myostatin. However, little is known of the long-term effects on muscle of myostatin blockade. To evaluate potential sequelae from the prolonged absence of myostatin, senescent myostatin null (mstn-/-) mice were studied. Senescent mstn-/- mice continue to have normal muscle with increased mass and strength relative to controls. Muscles of senescent mstn-/- mice regenerate robustly from both chronic and acute injury. Early markers of regeneration are enhanced in the absence of myostatin, suggesting a mechanism for the attenuation of dystrophic features found in mdx mice lacking myostatin.
Wagner
Kathryn R
KR
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. kwagner@jhmi.edu
Liu
Xiaosong
X
Chang
Xiaoli
X
Allen
Ronald E
RE
D000375:Aging / Q000473:pathology; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D049109:Cell Proliferation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000293:injuries / Q000473:pathology / Q000502:physiology*; D055435:Myostatin; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta