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Rho-GEF trio regulates osteoclast differentiation and function by Rac1/Cdc42
- Source :
- Experimental Cell Research. 396:112265
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
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.
- Subjects :
- Male
rac1 GTP-Binding Protein
0301 basic medicine
p38 mitogen-activated protein kinases
Regulator
Osteoclasts
RAC1
CDC42
Protein Serine-Threonine Kinases
Biology
p38 Mitogen-Activated Protein Kinases
Monocytes
Bone resorption
Mice
03 medical and health sciences
0302 clinical medicine
PAK1
Osteogenesis
Osteoclast
Conditional gene knockout
medicine
Animals
Guanine Nucleotide Exchange Factors
Femur
Bone Resorption
cdc42 GTP-Binding Protein
Mice, Knockout
Macrophage Colony-Stimulating Factor
Neuropeptides
RANK Ligand
Cell Differentiation
Cell Biology
Phosphoproteins
Cell biology
Mice, Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
030220 oncology & carcinogenesis
Female
Signal Transduction
Subjects
Details
- ISSN :
- 00144827
- Volume :
- 396
- Database :
- OpenAIRE
- Journal :
- Experimental Cell Research
- Accession number :
- edsair.doi.dedup.....4e51f16506f78d7fdad04915888aeee8