Avian osteoclasts as estrogen target cells

Merry Jo Oursler, Philip Osdoby, Joan Pyfferoen, B. Lawrence Riggs, Thomas C. Spelsberg

Research output: Contribution to journalArticle

304 Scopus citations

Abstract

Although in vivo effects of 17β-estradiol (estrogen) on bone turnover have been shown to occur mainly through influences on osteoclast-mediated bone resorption, the mechanism by which estrogen reduces bone resorption is unclear. To approach this question, we have examined authentic osteoclasts for evidence of a direct osteoclast response to estrogen in vitro. Highly purified (>90%) viable avian osteoclasts from birds maintained on a low calcium diet were obtained using an osteoclast-specific monoclonal antibody coupled to magnetic beads. Isolated cells were either analyzed directly for estrogen receptor (ER) levels or cultured to assess the biological effects of estrogen. Northern blot analysis revealed a 5.2-kilobase mRNA that hybridized with a cDNA to human ER mRNA in the osteoclasts. An anti-human ER antibody recognized proteins of 66 kDa and 140 kDa in osteoclast extracts by Western blot analysis. The 66-kDa size is in close agreement with the reported size of the human ER. Nuclear binding of estrogen to intact viable osteoclasts was steroid-specific and saturable, with 5662 ± 1420 molecules bound per nucleus (mean ± SEM). In vitro estrogen responses in osteoclasts included a dose-dependent decrease in resorption as well as an increase in nuclear protooncogene mRNA levels. These observations indicate that osteoclasts are capable of directly responding to estrogen in vivo.

Original languageEnglish (US)
Pages (from-to)6613-6617
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number15
DOIs
StatePublished - Aug 1 1991

Keywords

  • Bone resorption
  • Protooncogene expression
  • Steroid hormone
  • Steroid receptor

ASJC Scopus subject areas

  • General

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