title: A soluble activin type IIA receptor induces bone formation and improves skeletal integrity.
abstract: Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-beta superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-beta signaling ligand, is present at high levels in bone and may play a role in the regulation of bone metabolism. Here we demonstrate that pharmacological blockade of ligand signaling through the high affinity receptor for activin, type II activin receptor (ActRIIA), by administration of the soluble extracellular domain of ActRIIA fused to a murine IgG2a-Fc, increases bone formation, bone mass, and bone strength in normal mice and in ovariectomized mice with established bone loss. These observations support the development of this pharmacological strategy for the treatment of diseases with skeletal fragility.
authors.affiliation: Acceleron Pharma, Inc., 149 Sidney Street, Cambridge, MA 02139, USA. spearsall@acceleronpharma.com
authors.forename: R Scott
authors.initials: RS
authors.lastname: Pearsall
authors.forename: Ernesto
authors.initials: E
authors.lastname: Canalis
authors.forename: Milton
authors.initials: M
authors.lastname: Cornwall-Brady
authors.forename: Kathryn W
authors.initials: KW
authors.lastname: Underwood
authors.forename: Brendan
authors.initials: B
authors.lastname: Haigis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Ucran
authors.forename: Ravindra
authors.initials: R
authors.lastname: Kumar
authors.forename: Eileen
authors.initials: E
authors.lastname: Pobre
authors.forename: Asya
authors.initials: A
authors.lastname: Grinberg
authors.forename: Eric D
authors.initials: ED
authors.lastname: Werner
authors.forename: Vaida
authors.initials: V
authors.lastname: Glatt
authors.forename: Lisa
authors.initials: L
authors.lastname: Stadmeyer
authors.forename: Deanna
authors.initials: D
authors.lastname: Smith
authors.forename: Jasbir
authors.initials: J
authors.lastname: Seehra
authors.forename: Mary L
authors.initials: ML
authors.lastname: Bouxsein
mesh_terms: D030301:Activin Receptors, Type II / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001696:Biomechanical Phenomena; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects*; D002460:Cell Line; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D008159:Lumbar Vertebrae / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D012995:Solubility / Q000187:drug effects
chemical_list: D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A