Glucocorticoids and the osteoclast

Hyun Ju Kim, Haibo Zhao, Hideki Kitaura, Sandip Bhattacharyya, Judson A. Brewer, Louis J. Muglia, F. Patrick Ross, Steven L. Teitelbaum

Research output: Chapter in Book/Report/Conference proceedingConference contribution

40 Citations (Scopus)

Abstract

Glucocorticoid (GC)-induced bone loss is the most common cause of secondary osteoporosis but its pathogenesis is controversial. GCs clearly suppress bone formation in vivo but the means by which they impact osteoblasts is unclear. Because bone remodeling is characterized by tethering of the activities of the two cells, the osteoclast is a potential modulator of the effect of GCs on osteoblasts. To address this issue we compared the effects of dexamethasone on wild-type (WT) osteoclasts with those derived from mice with disruption of the GC receptor in osteoclast lineage cells and found that the bone-degrading capacity of GC-treated WT cells is suppressed. The inhibitory effect of dexamethasone on bone resorption reflects failure of osteoclasts to organize their cytoskeleton in response to M-CSF. Dexamethasone specifically arrests M-CSF activation of RhoA, Rac, and Vav3, each of which regulate the osteoclast cytoskeleton. In all circumstances, mice lacking the GC receptor in osteoclast lineage cells are spared the impact of dexamethasone on osteoclasts and their precursors. Consistent with osteoclasts modulating the osteoblast-suppressive effect of dexamethasone, GC receptor-deficient mice are protected from the steroid's inhibition of bone formation.

Original languageEnglish
Title of host publicationSkeletal Biology and Medicine, Part A
Subtitle of host publicationAspects of Bone Morphogenesis and Remodeling
PublisherBlackwell Publishing Inc.
Pages335-339
Number of pages5
ISBN (Print)9781573316842
DOIs
Publication statusPublished - 2007 Nov
Externally publishedYes

Publication series

NameAnnals of the New York Academy of Sciences
Volume1116
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Bone remodeling
  • Glucocorticoids
  • Osteoclasts

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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  • Cite this

    Kim, H. J., Zhao, H., Kitaura, H., Bhattacharyya, S., Brewer, J. A., Muglia, L. J., Patrick Ross, F., & Teitelbaum, S. L. (2007). Glucocorticoids and the osteoclast. In Skeletal Biology and Medicine, Part A: Aspects of Bone Morphogenesis and Remodeling (pp. 335-339). (Annals of the New York Academy of Sciences; Vol. 1116). Blackwell Publishing Inc.. https://doi.org/10.1196/annals.1402.057