POLR2A blocks osteoclastic bone resorption and protects against osteoporosis by interacting with CREB1

文献类型： 外文期刊

第一作者： Liu, Chuxiao

作者： Liu, Chuxiao;Li, Bo;Xu, Liwen;Li, Guangyu;Han, Yu;Zhao, Xingyu;Li, Bo;Li, Dongsong

作者机构：

关键词： bone resorption; CREB1; osteoclastogenesis; osteoporosis; POLR2A

期刊名称：JOURNAL OF CELLULAR PHYSIOLOGY （ 影响因子：6.384； 五年影响因子：5.987 ）

ISSN： 0021-9541

年卷期： 2021 年 236 卷 7 期

页码：

收录情况： SCI

摘要： Bone-resorbing osteoclasts significantly contribute to osteoporosis, and understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss. Here, we report that POLR2A is upregulated during osteoclastogenesis. Functional analyses showed that the inhibition of POLR2A decreased osteoclastogenesis, whereas the overexpression of POLR2A had completely opposite effects in vitro. Notably, the osteoclast-specific deletion of POLR2A blocks bone resorption in vivo. Furthermore, POLR2A loss-of-function suppresses estrogen deficiency-induced bone resorption. Mechanistically, POLR2A regulates the assembly of CREB1 on the regulatory elements of its target genes. Collectively, using genetic, pharmacological, and disease mouse models, we have identified a previously undescribed protein that interacts with CREB1 to regulate osteoclastic bone resorption.

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