title: Increased muscle force production and bone mineral density in ActRIIB-Fc-treated mature rodents.
abstract: Myostatin is a highly conserved member of the transforming growth factor-β ligand family known to regulate muscle growth via activation of activin receptors. A fusion protein consisting of the extracellular ligand-binding domain of activin type IIB receptor with the Fc portion of human immunoglobulin G (ActRIIB-Fc) was used to inhibit signaling through this pathway. Here, we study the effects of this fusion protein in adult, 18-month-old, and orchidectomized mice. Significant muscle growth and enhanced muscle function were observed in adult mice treated for 3 days with ActRIIB-Fc. The ActRIIB-Fc-treated mice had enhanced fast fatigable muscle function, with only minor enhancement of fatigue-resistant fiber function. The ActRIIB-Fc-treated 18-month-old mice and orchidectomized mice showed significantly improved muscle function. Treatment with ActRIIB-Fc also increased bone mineral density and serum levels of a marker of bone formation. These observations highlight the potential of targeting ActRIIB receptor to treat age-related and hypogonadism-associated musculoskeletal degeneration.
authors.affiliation: Merck Research Laboratories, 126 E Lincoln Ave., RY80T-A100, Rahway, NJ 07065. hilary.wilkinson@merck.com.
authors.forename: Chi-Sung
authors.initials: CS
authors.lastname: Chiu
authors.forename: Norbert
authors.initials: N
authors.lastname: Peekhaus
authors.forename: Hans
authors.initials: H
authors.lastname: Weber
authors.forename: Sharon
authors.initials: S
authors.lastname: Adamski
authors.forename: Edward M
authors.initials: EM
authors.lastname: Murray
authors.forename: Hai Zhuan
authors.initials: HZ
authors.lastname: Zhang
authors.forename: Jing Zhang
authors.initials: JZ
authors.lastname: Zhao
authors.forename: Robin
authors.initials: R
authors.lastname: Ernst
authors.forename: Janet
authors.initials: J
authors.lastname: Lineberger
authors.forename: Lingyi
authors.initials: L
authors.lastname: Huang
authors.forename: Richard
authors.initials: R
authors.lastname: Hampton
authors.forename: Beth Anne
authors.initials: BA
authors.lastname: Arnold
authors.forename: Salvatore
authors.initials: S
authors.lastname: Vitelli
authors.forename: Lora
authors.initials: L
authors.lastname: Hamuro
authors.forename: Wei-Rong
authors.initials: WR
authors.lastname: Wang
authors.forename: Nan
authors.initials: N
authors.lastname: Wei
authors.forename: Greg M
authors.initials: GM
authors.lastname: Dillon
authors.forename: Jiangyong
authors.initials: J
authors.lastname: Miao
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Alves
authors.forename: Helmut
authors.initials: H
authors.lastname: Glantschnig
authors.forename: Fubao
authors.initials: F
authors.lastname: Wang
authors.forename: Hilary A
authors.initials: HA
authors.lastname: Wilkinson
mesh_terms: D030301:Activin Receptors, Type II / Q000378:metabolism / Q000494:pharmacology*; D000375:Aging / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D057809:HEK293 Cells; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D055435:Myostatin / Q000378:metabolism; D009919:Orchiectomy; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D055948:Sarcopenia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D007141:Immunoglobulin Fc Fragments; C525912:Mstn protein, mouse; D055435:Myostatin; D010446:Peptide Fragments; D011347:Procollagen; D011993:Recombinant Fusion Proteins; C047202:procollagen Type I N-terminal peptide; D030301:Activin Receptors, Type II; C425584:activin receptor type II-B
keywords: Activin receptor type IIB; Muscle; Myostatin; Sarcopenia