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Estrogen protects primary osteocytes against glucocorticoid-induced apoptosis

På svenska

Author

  • G Gu
  • T A Hentunen
  • M Nars
  • Pirkko Härkönen
  • H K Väänänen

Summary, in English

Glucocorticoid-induced osteoporosis may be at least in part due to the increased apoptosis of osteocytes. To study the role of osteocyte apoptosis in glucocorticoid-induced osteoporosis, we isolated primary osteocytes from murine calvaria for the analysis of the effects of dexamethasone in in vitro culture. The cells were identified by morphology, cytochemical staining, immunocytochemical staining and mRNA expression of phosphate-regulating gene with homology to endopeptidases on the X chromosome (PHEX) and sclerosteosis/van Buchem disease gene (SOST). We found that dexamethasone induced osteocyte apoptosis in a dose-dependent manner. A glucocorticoid receptor antagonist, mifepristone (RU486), suppressed dexamethasone-Induced osteocyte apoptosis, suggesting that it was mediated by glucocorticoid receptor. Immunocytochemical stainings showed that glucocorticoid receptors are present in primary osteocytes, and they were translocated to nuclei after the exposure to dexamethasone. Addition of estrogen prevented glucocorticoid receptor translocation into nuclei. Corresponding antiapoptotic effects in primary osteocytes were also seen after the pretreatment of primary osteocytes with a picomolar concentration of estrogen. The pure antiestrogen ICI 182,780 inhibited estrogen effect on apoptosis induced by dexamethasone. These data suggest that glucocorticoid receptors play an important role in glucocorticoid-induced osteocyte apoptosis. Most importantly, estrogen has a protective effect against osteocyte apoptosis. To conclude, the mechanism of glucocorticoid-induced osteoporosis may be due to the apoptosis of osteocytes, which can be opposed by estrogen.

Publishing year

2005

Language

English

Pages

583-595

Publication/Series

Apoptosis

Volume

10

Issue

3

Document type

Journal article

Publisher

Springer

Topic

  • Clinical Medicine
  • Cancer and Oncology

Keywords

  • osteoporosis
  • osteocyte
  • glucocorticoid
  • apoptosis
  • estrogen

Status

Published

ISBN/ISSN/Other

  • ISSN: 1360-8185