Control of bone mass and remodeling by PTH receptor signaling in osteocytes

Charles A. O'Brien, Lilian I. Plotkin, Carlo Galli, Joseph J. Goellner, Arancha R. Gortazar, Matthew R. Allen, Alexander G. Robling, Mary Bouxsein, Ernestina Schipani, Charles H. Turner, Robert L. Jilka, Robert S. Weinstein, Stavros C. Manolagas, Teresita Bellido

Research output: Contribution to journalArticle

272 Scopus citations

Abstract

Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation, Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and - independent mechanisms, respectively.

Original languageEnglish (US)
Article numbere2942
JournalPloS one
Volume3
Issue number8
DOIs
StatePublished - Aug 13 2008

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    O'Brien, C. A., Plotkin, L. I., Galli, C., Goellner, J. J., Gortazar, A. R., Allen, M. R., Robling, A. G., Bouxsein, M., Schipani, E., Turner, C. H., Jilka, R. L., Weinstein, R. S., Manolagas, S. C., & Bellido, T. (2008). Control of bone mass and remodeling by PTH receptor signaling in osteocytes. PloS one, 3(8), [e2942]. https://doi.org/10.1371/journal.pone.0002942