Bone Morphogenetic Protein-2 Desensitizes MC3T3-E1 Osteoblastic Cells to Estrogen Through Transcriptional Downregulation of Estrogen Receptor 1
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Background: Estrogens exert preferable effects on bone metabolism through two es-trogen receptors (ERs), ER1 and ER2, which activate the transcription of a set of genes as ligand-dependent transcription factors. Thus, growth factors and hormones which mod-ulate ER expression in the bone, if any, may possibly modulate the effect of estrogens on bone metabolism. However, research as to which of these molecules regulate the ex-pression of ERs in osteoblasts has not been well documented. Methods: A reporter as-say system developed in this study was used to explore molecules that modulate ER1expression in MC3T3-E1 osteoblastic cells. Gene expression was analyzed by reverse transcription-polymerase chain reaction. Results: A pilot study using the reporter sys-tem revealed that bone morphogenetic protein (BMP)-2 negatively regulated ER1, but not ER2, expression in MC3T3-E1 cells. Consistently, estradiol-induced reporter activity via an estrogen responsive element was strongly suppressed in MC3T3-E1 cells pretreat-ed with BMP-2. Conclusions: BMP-2 desensitizes osteoblastic cells to estrogen through downregulation of ER1 expression.
Abstract
Background: Estrogens exert preferable effects on bone metabolism through two es-trogen receptors (ERs), ER1 and ER2, which activate the transcription of a set of genes as ligand-dependent transcription factors. Thus, growth factors and hormones which mod-ulate ER expression in the bone, if any, may possibly modulate the effect of estrogens on bone metabolism. However, research as to which of these molecules regulate the ex-pression of ERs in osteoblasts has not been well documented. Methods: A reporter as-say system developed in this study was used to explore molecules that modulate ER1expression in MC3T3-E1 osteoblastic cells. Gene expression was analyzed by reverse transcription-polymerase chain reaction. Results: A pilot study using the reporter sys-tem revealed that bone morphogenetic protein (BMP)-2 negatively regulated ER1, but not ER2, expression in MC3T3-E1 cells. Consistently, estradiol-induced reporter activity via an estrogen responsive element was strongly suppressed in MC3T3-E1 cells pretreat-ed with BMP-2. Conclusions: BMP-2 desensitizes osteoblastic cells to estrogen through downregulation of ER1 expression.
참고문헌 (24)
- Turner RT, "Skeletal effects of estrogen", Endocr Rev, 15, pp.275~300 (1994)
- Khosla S, "Estrogen and the skeleton", Trends Endocrinol Metab, 23, pp.576~581 (2012)
- Venken K, "Sex hormones, their receptors and bone health", Osteoporos Int, 19, pp.1517~1525 (2008)
- Bland R, "Steroid hormone receptor expression and action in bone", Clin Sci (Lond), 98, pp.217~240 (2000)
- Nilsson S, "Estrogen receptors: therapies targeted to receptor subtypes", Clin Pharmacol Ther, 89, pp.44~55 (2011)
- Heldring N, "Estrogen receptors: how do they signal and what are their targets", Physiol Rev, 87, pp.905~931 (2007)
- Ishibashi O, "Tamoxifen agonism and estrogen antagonism of c-fos gene promoter activity through non-consensus-responsive elements in MC3T3-E1 osteoblasts", Biochem Biophys Res Commun, 289, pp.705~711 (2001)
- Hewitt SC, "Oestrogen receptor knockout mice: roles for oestrogen receptors alpha and beta in reproductive tissues", Reproduction, 125, pp.143~149 (2003)
- Emmen JM, "Estrogen receptor knockout mice: phenotypes in the female reproductive tract", Gynecol Endocrinol, 17, pp.169~176 (2003)
- McCauley LK, "Estrogen receptors in skeletal metabolism: lessons from genetically modified models of receptor function", Crit Rev Eukaryot Gene Expr, 12, pp.89~100 (2002)
- Hawse JR, "Estrogen-TGFbeta cross-talk in bone and other cell types: role of TIEG, Runx2, and other transcription factors", J Cell Biochem, 103, pp.383~392 (2008)
- Matsuda T, "Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3", J Biol Chem, 276, pp.42908~42914 (2001)
- Wu L, "Smad4 as a transcription corepressor for estrogen receptor alpha", J Biol Chem, 278, pp.15192~15200 (2003)
- Yamamoto T, "Cross-talk between bone morphogenic proteins and estrogen receptor signaling", Endocrinology, 143, pp.2635~2642 (2002)
- Yamamoto T, "Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling", FEBS Lett, 486, pp.143~148 (2000)
- Ishibashi O, "Cloning and characterization of the functional promoter of mouse estrogen receptor beta gene", Biochim Biophys Acta, 1519, pp.223~229 (2001)
- Kato S, "Molecular mechanism of a cross-talk between oestrogen and growth factor signalling pathways", Genes Cells, 5, pp.593~601 (2000)
- Stoica A, "Regulation of estrogen receptor-alpha gene expression by 1, 25-dihydroxyvitamin D in MCF-7 cells", J Cell Biochem, 75, pp.640~651 (1999)
- Swami S, "1alpha,25-Dihydroxyvitamin D3 down-regulates estrogen receptor abundance and suppresses estrogen actions in MCF-7 human breast cancer cells", Clin Cancer Res, 6, pp.3371~3379 (2000)
- Lonard DM, "The 26S proteasome is required for estrogen receptor-alpha and coactivator turnover and for efficient estrogen receptor-alpha transactivation", Mol Cell, 5, pp.939~948 (2000)
- Reid G, "Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling", Mol Cell, 11, pp.695~707 (2003)
- Ihionkhan CE, "Estrogen causes dynamic alterations in endothelial estrogen receptor expression", Circ Res, 91, pp.814~820 (2002)
- Tschugguel W, "Differential regulation of proteasome-dependent estrogen receptor alpha and beta turnover in cultured human uterine artery endothelial cells", J Clin Endocrinol Metab, 88, pp.2281~2287 (2003)
- Matsumoto Y, "Estrogen facilitates osteoblast differentiation by upregulating bone morphogenetic protein-4 signaling", Steroids, 78, pp.513~520 (2013)