Introduction: Estrogen therapy decreases circulating levels of sclerostin, a protein product of SOST which increase in postmenopausal women. However, the mechanisms of estrogen on the expression of SOST remain unclear. This study was hypothesized that estrogen modulates SOST expression by interfering bone morphogenic protein (BMP) signaling on the basis that BMP is an inducer of SOST in osteoblasts.
Description of methods: We investigated the expression of SOST and other BMP-2 responsive genes in the treatment either with BMP-2 (200 ng/ml), estrogen (100 nM), or combination of both using female-originated human mesenchymal stromal cells (hMSCs) by real time RT-PCR or ELISA. Molecular mechanism was examined using the inhibitor of Wnt (ICI 182, 780: 100 nM) and Smad pathway (AMPK: 10 μM).
Results: There was no direct effect of estrogen on SOST expression, but estrogen significantly down-regulated SOST expression which was induced by BMP-2. Treatment with Wnt signaling inhibitor did not affect SOST induction by BMP-2, but counteracted the suppressive effect of estrogen on SOST induction by BMP-2. On the contrary, Smad inhibitor completely blocked SOST induction by BMP-2. This tendency repeated in the expression of other BMP-2 responsive genes such as alkaline phosphatase, BMP-2, or IGF1.
Conclusions: Current findings suggest that estrogen regulated SOST expression by cross-talk with BMP-2 signaling. Estrogen suppressed SOST induction by BMP-2 through Wnt signaling.
18 - 21 May 2013
European Calcified Tissue Society