title: Inhibition of myostatin in adult mice increases skeletal muscle mass and strength.
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.
authors.affiliation: Musculoskeletal Sciences Department, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. lwhittemore@wyeth.com
authors.forename: Lisa-Anne
authors.initials: LA
authors.lastname: Whittemore
authors.forename: Kening
authors.initials: K
authors.lastname: Song
authors.forename: Xiangping
authors.initials: X
authors.lastname: Li
authors.forename: Jane
authors.initials: J
authors.lastname: Aghajanian
authors.forename: Monique
authors.initials: M
authors.lastname: Davies
authors.forename: Stefan
authors.initials: S
authors.lastname: Girgenrath
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Hill
authors.forename: Mary
authors.initials: M
authors.lastname: Jalenak
authors.forename: Pamela
authors.initials: P
authors.lastname: Kelley
authors.forename: Andrea
authors.initials: A
authors.lastname: Knight
authors.forename: Rich
authors.initials: R
authors.lastname: Maylor
authors.forename: Denise
authors.initials: D
authors.lastname: O'Hara
authors.forename: Adele
authors.initials: A
authors.lastname: Pearson
authors.forename: Amira
authors.initials: A
authors.lastname: Quazi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ryerson
authors.forename: Xiang Yang
authors.initials: XY
authors.lastname: Tan
authors.forename: Kathleen N
authors.initials: KN
authors.lastname: Tomkinson
authors.forename: Geertruida M
authors.initials: GM
authors.lastname: Veldman
authors.forename: Angela
authors.initials: A
authors.lastname: Widom
authors.forename: Jill F
authors.initials: JF
authors.lastname: Wright
authors.forename: Steve
authors.initials: S
authors.lastname: Wudyka
authors.forename: Liz
authors.initials: L
authors.lastname: Zhao
authors.forename: Neil M
authors.initials: NM
authors.lastname: Wolfman
mesh_terms: 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*
chemical_list: D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta