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Research Article Free access | 10.1172/JCI119880

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

D J Rickard, L C Hofbauer, S K Bonde, F Gori, T C Spelsberg, and B L Riggs

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

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Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

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Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

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Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

Find articles by Gori, F. in: PubMed | Google Scholar

Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

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Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905, USA.

Find articles by Riggs, B. in: PubMed | Google Scholar

Published January 15, 1998 - More info

Published in Volume 101, Issue 2 on January 15, 1998
J Clin Invest. 1998;101(2):413–422. https://doi.org/10.1172/JCI119880.
© 1998 The American Society for Clinical Investigation
Published January 15, 1998 - Version history
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Abstract

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 ( approximately 800 ER/ nucleus) and at high ( approximately 3, 900 ER/nucleus) levels, respectively. As assessed by reverse transcriptase PCR, treatment with 17beta-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-beta1 and -beta2 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. 17beta-estradiol increased BMP-6 protein production sixfold by Western analysis. Cotreatment with antiestrogens (ICI 182,780 or 4-hydroxytamoxifen) antagonized the effects of 17beta-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.

Version history
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