Bone morphogenetic protein-6 production in human osteoblastic cell lines: Selective regulation by estrogen

David J. Rickard, Lorenz C. Hofbauer, Susan K. Bonde, Francesca Gori, Thomas C. Spelsberg, B. Lawrence Riggs

Research output: Contribution to journalArticlepeer-review

80 Scopus citations


Bone morphogenetic proteins (BMPs) induce differentiation of osteoblast and chondroblast lineage cells from uncommitted mesenchymal precursors. Because estrogen has potent osteochondrogenic actions, we investigated its effect on BMP production in two estrogen-responsive, human immortalized cell lines (hFOB/ER3 and hFOB/ER9) that display the mature osteoblast phenotype. These cell lines were produced by stable transfection of the estrogen receptor (ER) gene into immortalized fetal osteoblasts at low (~ 800 ER/nucleus) and at high (~ 3,900 ER/nucleus) levels, respectively. As assessed by reverse transcriptase PCR, treatment with 17β-estradiol (10- 10 - 10-7 M) increased steady-state levels of BMP-6 mRNA dose dependently by twofold in the hFOB/ER3 cells and by over threefold in the hFOB/ER9 cells. Messenger RNA levels for transforming growth factors-β1 and -β2 and BMPs- 1 through -5 and -7 levels were unchanged. The results were confirmed by sequence determination of the PCR product and by Northern blot analysis for total RNA. 17β-estradiol increased BMP-6 protein production sixfold by Western analysis. Cotreatment with antiestrogens (ICI 182,780 or 4- hydroxytamoxifen) antagonized the effects of 17β-estradiol. These data suggest that some of the skeletal effects of estrogen on bone and cartilage may be mediated by increased production of BMP-6 by osteoblasts.

Original languageEnglish (US)
Pages (from-to)413-422
Number of pages10
JournalJournal of Clinical Investigation
Issue number2
StatePublished - Jan 15 1998


  • Antiestrogens
  • BMP
  • Differentiation
  • Estrogen
  • Osteoblasts

ASJC Scopus subject areas

  • General Medicine


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