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Bone Abstracts (2014) 3 PP129 | DOI: 10.1530/boneabs.3.PP129

Cell biology: osteoblasts and bone formation

Modulation of sclerostin expression by estrogen via BMP-2 signaling in human mesenchymal stromal cells and osteoblasts

Ri Youn Kim1, Hoon Joo Yang2, Yun Mi Song3, Tae Hyung Cho3, Soon Jung Hwang1,2 & In Sook Kim3

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1Department of Maxillofacial Cell and Developmental Biology, Seoul, Republic of Korea; 2Department of Oral and Maxillofacial Surgery, Seoul, Republic of Korea; 3Dental Research Institute, Seoul, Republic of Korea.


Little is known about the molecular mechanisms underlying the interaction between Sclerostin (SOST) and estrogen, showing an inverse relation in clinical data. Therefore, we investigated mechanisms by which estrogen modulates Sost expression at human osteoblastic cell level in association with BMP-2 signaling, which is a potential route of SOST induction. BMP-2 significantly induced SOST expression, which is suppressed by 17β-estradiol (E2) in human mesenchymal stromal cells (hMSCs) and mandible-derived osteoblasts from female donors, despite non-effect of E2 alone on SOST expression. E2 increased transcriptional activity of β-catenin/TCF/LEF responsive vector, which is suppressed by the combined treatment of BMP-2 and E2 in hMSCs. Either estrogen receptor (ER)α antagonist or silencing of ERα gene did counteract the suppressive effect of E2 on SOST induction by BMP-2, while it had no effect on the activity of BMP-2 alone BMP-2. However, E2 had non-effect on the transcriptional activity of Smad4, which was but dependent of BMP-2. SOST expression pattern from human osteoblasts was in particular correlated with the relative ratio of RANKL to OPG expression. Taken together, these findings showed that estrogen negatively modulates SOST expression coupled with BMP-2 signaling, which involve Wnt pathway via ERα and β-catenin, providing insight into how estrogen is anabolic to bone at the level of osteoblastic cells.

Keywords: Estrogen, sclerostin, BMP-2, human mesenchymal stromal cells, human osteoblasts, Wnt pathway, estrogen receptor α, RANKL/OPG

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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