破骨细胞
骨吸收
RAC1
CDC42型
条件基因敲除
生物
吸收
细胞生物学
GTP酶
骨重建
内分泌学
内科学
信号转导
表型
基因
体外
遗传学
医学
作者
Jiawen Gu,Zhiwen Yang,Lichan Yuan,Shuyu Guo,Dan Wang,Na Zhao,Meng Li,Haojie Liu,Wenjing Chen,Junqing Ma
标识
DOI:10.1016/j.yexcr.2020.112265
摘要
Many bone diseases result from abnormal bone resorption by osteoclasts (OCs). Studying OC related regulatory genes is necessary for the development of new therapeutic strategies. Rho GTPases have been proven to regulate OC differentiation and function and only mature OCs can carry out bone resorption. Here we demonstrate that Rac1 and Cdc42 exchange factor Triple functional domain (Trio) is critical for bone resorption caused by OCs. In this study, we created LysM-Cre;Triofl/fl conditional knockout mice in which Trio was conditionally ablated in monocytes. LysM-Cre;Triofl/fl mice showed increased bone mass due to impaired bone resorption caused by OCs. Furthermore, our in vitro analysis indicated that Trio conditional deficiency significantly suppressed OC differentiation and function. At the molecular level, Trio deficiency significantly inhibited the expression of genes critical for osteoclastogenesis and OC function. Mechanistically, our researches suggested that perturbed Rac1/Cdc42-PAK1-ERK/p38 signaling could be used to explain the lower ability of bone resorption in CKO mice. Taken together, this study indicates that Trio is a regulator of OCs. Studying the role of Trio in OCs provides a potential new insight for the treatment of OC related bone diseases.
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