A soluble activin type IIA receptor induces bone formation and improves skeletal integrity

doi:10.1073/pnas.0711263105

A soluble activin type IIA receptor induces bone formation and improves skeletal integrity

*Acceleron Pharma, Inc., 149 Sidney Street, Cambridge, MA 02139;
^‡Department of Research, St. Francis Hospital and Medical Center, 114 Woodland Street, Hartford, CT 06105; and
^§Orthopedic Biomechanics Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215

Edited by John T. Potts, Jr., Massachusetts General Hospital, Charlestown, MA, and approved March 21, 2008 (received for review November 29, 2007)

Abstract

Diseases that affect the regulation of bone turnover can lead to skeletal fragility and increased fracture risk. Members of the TGF-β superfamily have been shown to be involved in the regulation of bone mass. Activin A, a TGF-β 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.

Footnotes

^†To whom correspondence should be addressed. E-mail: spearsall{at}acceleronpharma.com
Author contributions: R.S.P., R.K., A.G., E.D.W., and M.L.B. designed research; R.S.P., E.C., M.C.-B., E.P., A.G., E.D.W., V.G., L.S., D.S., and M.L.B. performed research; K.W.U., B.H., and J.U. contributed new reagents/analytic tools; R.S.P., E.C., M.C.-B., R.K., E.P., A.G., E.D.W., V.G., L.S., D.S., and M.L.B. analyzed data; and R.S.P. and J.S. wrote the paper.
Conflict of interest statement: R.S.P., M.C.-B., K.W.U., B.H., J.U., R.K., E.P., A.G., E.D.W., and J.S. are full-time employees of Acceleron Pharma.
This article is a PNAS Direct Submission.
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