A soluble activin type IIA receptor induces bone formation and improves skeletal integrity.
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.
Pearsall
R Scott
RS
Acceleron Pharma, Inc., 149 Sidney Street, Cambridge, MA 02139, USA. spearsall@acceleronpharma.com
Canalis
Ernesto
E
Cornwall-Brady
Milton
M
Underwood
Kathryn W
KW
Haigis
Brendan
B
Ucran
Jeffrey
J
Kumar
Ravindra
R
Pobre
Eileen
E
Grinberg
Asya
A
Werner
Eric D
ED
Glatt
Vaida
V
Stadmeyer
Lisa
L
Smith
Deanna
D
Seehra
Jasbir
J
Bouxsein
Mary L
ML
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
D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A