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

R. Scott Pearsall, Ernesto Canalis, Milton Cornwall-Brady, Kathryn W. Underwood, Brendan Haigis, Jeffrey Ucran, Ravindra Kumar, Eileen Pobre, Asya Grinberg, Eric D. Werner, Vaida Glatt, Lisa Stadmeyer, Deanna Smith, Jasbir Seehra, Mary L. Bouxsein

Research output: Contribution to journalArticle

137 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7082-7087
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number19
DOIs
StatePublished - May 13 2008

Keywords

  • Anabolic
  • Osteoporosis
  • TGF-β
  • Therapeutic

ASJC Scopus subject areas

  • General

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    Pearsall, R. S., Canalis, E., Cornwall-Brady, M., Underwood, K. W., Haigis, B., Ucran, J., Kumar, R., Pobre, E., Grinberg, A., Werner, E. D., Glatt, V., Stadmeyer, L., Smith, D., Seehra, J., & Bouxsein, M. L. (2008). A soluble activin Type IIA receptor induces bone formation and improves skeletal integrity. Proceedings of the National Academy of Sciences of the United States of America, 105(19), 7082-7087. https://doi.org/10.1073/pnas.0711263105