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;Trio^fl/fl conditional knockout mice in which Trio was conditionally ablated in monocytes. LysM-Cre;Trio^fl/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.

许多骨病是由破骨细胞（OCs）引起的异常骨吸收引起的。研究与OC有关的调节基因对于开发新的治疗策略是必要的。Rho GTPases已被证明可调节OC的分化和功能，只有成熟的OC才能进行骨吸收。在这里，我们证明Rac1和Cdc42交换因子三重功能域（Trio）对于由OCs引起的骨吸收至关重要。在这项研究中，我们创建了LysM-Cre; Trio ^{fl / fl}条件敲除小鼠，其中Trio在单核细胞中被条件消融。LysM-Cre; Trio ^{fl / fl}小鼠显示出骨质增加，这是由于OCs引起的骨吸收受损所致。此外，我们的体外分析表明，Trio条件缺陷明显抑制了OC的分化和功能。在分子水平上，三重缺陷明显抑制了破骨细胞生成和OC功能的关键基因的表达。从机理上讲，我们的研究表明，受干扰的Rac1 / Cdc42-PAK1-ERK / p38信号传导可用于解释CKO小鼠骨吸收能力低下。两者合计，这项研究表明Trio是OC的监管者。研究Trio在OC中的作用为治疗OC相关的骨病提供了潜在的新见解。