Activating transcription factor 4 is critical for proliferation and survival in primary bone marrow stromal cells and calvarial osteoblasts.

Journal of Cellular Biochemistry
Xiaoyan ZhangGuozhi Xiao

Abstract

Activating transcription factor 4 (ATF4) is essential for bone formation. However, the mechanism of its actions in bone is poorly understood. The present study examined the role for ATF4 in the regulation of proliferation and survival of primary mouse bone marrow stromal cells (BMSCs) and osteoblasts. Results showed that Atf4(-/-) cells display a severe proliferative defect as measured by multiple cell proliferation assays. Cell cycle progression of Atf4(-/-) BMSCs was largely delayed with significant G1 arrest. Expression of cyclin D1 was decreased both at the mRNA and protein level. A similar proliferation defect was observed in Atf4(-/-) calvarial periosteal osteoblasts when compared with wt control. Knocking down Atf4 mRNA by small interfering RNA in MC3T3-E1 subclone 4 preosteoblasts markedly reduced expression of cyclin D1 and cell proliferation. In contrast, overexpression of ATF4 increased cyclin D1 expression as well as cell proliferation in Atf4(-/-) BMSCs. In addition, apoptosis was significantly increased in Atf4(-/-) BMSCs and calvarial periosteal osteoblasts relative to wt controls. Taken together, these results for the first time demonstrate that ATF4 is a critical regulator of proliferation and survival in BMSCs...Continue Reading

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Citations

Jul 16, 2010·The Journal of Clinical Investigation·Huiling CaoGuozhi Xiao
Mar 16, 2013·International Journal of Biological Sciences·Shibing YuGuozhi Xiao
Aug 27, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Chui-Feng FanEn-Hua Wang
May 8, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Ke ZhuGuozhi Xiao
Jul 8, 2015·Nature Communications·Chuanyue WuGuozhi Xiao
Dec 12, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Giuseppina StorlinoMaria Grano
Jul 28, 2013·The Journal of Biological Chemistry·Guozhi XiaoH Henry Dong
Jan 15, 2020·Bone Research·Huiling CaoGuozhi Xiao
Feb 5, 2015·The Journal of Biological Chemistry·Ke ZhuGuozhi Xiao
Jan 2, 2021·Bone Research·Huiling CaoGuozhi Xiao

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