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Biochem Biophys Res Commun ; 300(4): 965-71, 2003 Jan 24.
Article in English | MEDLINE | ID: mdl-12559968

ABSTRACT

A human therapeutic that specifically modulates skeletal muscle growth would potentially provide a benefit for a variety of conditions including sarcopenia, cachexia, and muscular dystrophy. Myostatin, a member of the TGF-beta family of growth factors, is a known negative regulator of muscle mass, as mice lacking the myostatin gene have increased muscle mass. Thus, an inhibitor of myostatin may be useful therapeutically as an anabolic agent for muscle. However, since myostatin is expressed in both developing and adult muscles, it is not clear whether it regulates muscle mass during development or in adults. In order to test the hypothesis that myostatin regulates muscle mass in adults, we generated an inhibitory antibody to myostatin and administered it to adult mice. Here we show that mice treated pharmacologically with an antibody to myostatin have increased skeletal muscle mass and increased grip strength. These data show for the first time that myostatin acts postnatally as a negative regulator of skeletal muscle growth and suggest that myostatin inhibitors could provide a therapeutic benefit in diseases for which muscle mass is limiting.


Subject(s)
Muscle, Skeletal/growth & development , Transforming Growth Factor beta/antagonists & inhibitors , Transforming Growth Factor beta/metabolism , Amino Acid Sequence , Animals , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal/immunology , Body Weight , CHO Cells , Cricetinae , Culture Media, Conditioned , Female , Hand Strength , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Muscle Fibers, Skeletal/cytology , Muscle, Skeletal/anatomy & histology , Muscle, Skeletal/physiology , Myostatin , Protein Binding , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/immunology
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