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    Mol Endocrinol. 2000 May;14(5):623-33.

    Antiestrogens specifically up-regulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells.

    van den Wijngaard A, Mulder WR, Dijkema R, Boersma CJ, Mosselman S, van Zoelen EJ, Olijve W.

    Department of Applied Biology, University of Nijmegen, The Netherlands.

    Bone morphogenetic protein-4 (BMP-4) plays an important role in the onset of endochondral bone formation in humans, and a reduction in BMP-4 expression has been associated with a variety of bone diseases. Here we describe, by transient transfection assays in bone cells, that the human BMP-4 promoter recently characterized in our laboratory can be stimulated specifically by antiestrogens but not by estrogens or other steroid hormones. This activity is dependent on the presence of the estrogen receptor (ER)-alpha, although the promoter lacks a consensus estrogen-responsive element. No activity was observed in the presence of ERbeta, but synergy was observed when both ER subtypes were cotransfected. The observed stimulation of BMP-4 promoter activity by antiestrogens appeared bone cell specific and was reversed upon addition of estrogens. Since antiestrogens are known to be effective in hormone replacement therapies for postmenopausal women, this observation may help to develop new strategies for treatment and prevention of osteoporosis.

    PMID: 10809227 [PubMed - indexed for MEDLINE]

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