Glucocorticoids Hijack Runx2 to Stimulate Wif1 for Suppression of Osteoblast Growth and Differentiation.
Glucocorticoids Hijack Runx2 to Stimulate Wif1 for Suppression of Osteoblast Growth and Differentiation.
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DOI：
10.1002/jcp.25399
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发表时间：
2017-01
影响因子：
5.6
通讯作者：
Frenkel B
中科院分区：
文献类型：
--
作者：
Morimoto E;Li M;Khalid AB;Krum SA;Chimge NO;Frenkel B
Inhibition of Runx2 is one of many mechanisms that suppress bone formation in glucocorticoid (GC)-induced osteoporosis (GIO). We profiled mRNA expression in ST2/Rx2dox cells after treatment with doxycycline (dox; to induce Runx2) and/or the synthetic GC dexamethasone (dex). As expected, dex typically antagonized Runx2-driven transcription. Select genes, however, were synergistic stimulated and this was confirmed by RT-qPCR. Among the genes synergistically stimulated by GCs and Runx2 was Wnt inhibitory Factor 1 (Wif1), and Wif1 protein was readily detectable in medium conditioned by cultures co-treated with dox and dex, but neither alone. Cooperation between Runx2 and GCs in stimulating Wif1 was also observed in primary preosteoblast cultures. GCs strongly inhibited dox-driven alkaline phosphatase (ALP) activity in control ST2/Rx2dox cells, but not in cells in which Wif1 was silenced. Unlike its antimitogenic activity in committed osteoblasts, induction of Runx2 transiently increased the percentage of cells in S-phase and accelerated proliferation in the ST2 mesenchymal pluripotent cell culture model. Furthermore, like the inhibition of Runx2-driven ALP activity, dex antagonized the transient mitogenic effect of Runx2 in ST2/Rx2dox cultures, and this inhibition eased upon Wif1 silencing. Plausibly, homeostatic feedback loops that rely on Runx2 activation to compensate for bone loss in GIO are thwarted, exacerbating disease progression through stimulation of Wif1.
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影响因子：
5.6
作者：
Baniwal, Sanjeev K.;Little, Gillian H.;Chimge, Nyam-Osor;Frenkel, Baruch
通讯作者：
Frenkel, Baruch
DOI：
10.1002/jbmr.2287
发表时间：
2014-12
期刊：
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子：
--
作者：
Chen H;Ghori-Javed FY;Rashid H;Adhami MD;Serra R;Gutierrez SE;Javed A
通讯作者：
Javed A
影响因子：
64.8
作者：
Bhanot, P;Brink, M;Nusse, R
通讯作者：
Nusse, R
影响因子：
15.9
作者：
Kansara, Maya;Tsang, Michael;Thomas, David M.
通讯作者：
Thomas, David M.
DOI：
10.1073/pnas.96.25.14383
发表时间：
1999-12-07
影响因子：
11.1
作者：
Liu, XX;Liu, T;Wang, HY
通讯作者：
Wang, HY