Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells

Publication date: Available online 8 May 2018Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Yonatan Amzaleg, Jie Ji, Donlaporn Kittivanichkul, Anna E Törnqvist, Sara Windahl, Elias Sabag, Aysha B. Khalid, Hal Sternberg, Michael West, John A. Katzenellenbogen, Susan A. Krum, Nyam-Osor Chimge, Dustin E. Schones, Yankel Gabet, Claes Ohlsson, Baruch FrenkelAbstractEstrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17ß-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus-specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At ≥10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contra...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research