Rho-GEF trio regulates osteoclast differentiation and function by Rac1/Cdc42.
Exp Cell Res
; 396(1): 112265, 2020 11 01.
Article
em En
| MEDLINE
| ID: mdl-32898553
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoclastos
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Fosfoproteínas
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Reabsorção Óssea
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Neuropeptídeos
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Proteínas Serina-Treonina Quinases
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Proteína cdc42 de Ligação ao GTP
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Proteínas rac1 de Ligação ao GTP
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Fatores de Troca do Nucleotídeo Guanina
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Fêmur
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China