Inhibition of myostatin in adult mice increases skeletal muscle mass and strength.
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.
Whittemore
Lisa-Anne
LA
Musculoskeletal Sciences Department, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. lwhittemore@wyeth.com
Song
Kening
K
Li
Xiangping
X
Aghajanian
Jane
J
Davies
Monique
M
Girgenrath
Stefan
S
Hill
Jennifer J
JJ
Jalenak
Mary
M
Kelley
Pamela
P
Knight
Andrea
A
Maylor
Rich
R
O'Hara
Denise
D
Pearson
Adele
A
Quazi
Amira
A
Ryerson
Stephanie
S
Tan
Xiang Yang
XY
Tomkinson
Kathleen N
KN
Veldman
Geertruida M
GM
Widom
Angela
A
Wright
Jill F
JF
Wudyka
Steve
S
Zhao
Liz
L
Wolfman
Neil M
NM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology; D001835:Body Weight; D016466:CHO Cells; D006224:Cricetinae; D017077:Culture Media, Conditioned; D005260:Female; D018737:Hand Strength; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000254:growth & development* / Q000502:physiology; D055435:Myostatin; D011485:Protein Binding; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta