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. 2017 Apr 4;7:45686. doi: 10.1038/srep45686

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Copyright © 2017, The Author(s)

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

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The double asterisk indicates p < 0.05. Of note, A77 = A77636, and CN = control. (A) Decrease in the relative mRNA abundance of NFATc1, Cathepsin K, and TRAP in response to 5 and 10 μM A77363 in RANKL stimulated cells. (B) Downregulation of NFATc1, Cathepsin K, and TRAP proteins in response to 5 and 10 μM A77363 in RANKL stimulated cells. (C) Suppression of TRAP-positive multinucleated cells by 1–10 μM A77636. The number of TRAP-positive cells with 3 or more nuclei was counted. (D) Suppressive effects of ISRIB on A77636-driven downregulation of NFATc1 and Cat K. (E,F) Partial reduction of ATF4 mRNA and ATF4 protein, respectively, with siRNA specific to ATF4. (G) ATF4-mediated upregulation of osteocalcin (OCN) mRNA in response to 10 μM A77636.