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Rho-GEF trio regulates osteoclast differentiation and function by Rac1/Cdc42
Jiawen Gu1, Zhiwen Yang1, Lichan Yuan1
1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China; Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, China.
Experimental Cell Research
|September 8, 2020
Summary
Triple functional domain (Trio) is crucial for osteoclast (OC) function and bone resorption. Ablating Trio in monocytes impairs OC differentiation, leading to increased bone mass and offering new therapeutic targets for bone diseases.
Area of Science:
- Bone Biology
- Cell Signaling
- Molecular Genetics
Background:
- Abnormal bone resorption by osteoclasts (OCs) underlies many bone diseases.
- Understanding OC regulatory genes is vital for developing novel therapeutic strategies.
- Rho GTPases are known regulators of OC differentiation and function.
Purpose of the Study:
- To investigate the role of the Rac1 and Cdc42 exchange factor, Triple functional domain (Trio), in osteoclast-mediated bone resorption.
- To elucidate the molecular mechanisms by which Trio influences osteoclastogenesis and function.
Main Methods:
- Generation of LysM-Cre;Triofl/fl conditional knockout mice for Trio ablation in monocytes.
- In vitro analysis of osteoclast differentiation and function in Trio-deficient cells.
- Molecular analysis of gene expression and signaling pathways (Rac1/Cdc42-PAK1-ERK/p38).
Main Results:
- LysM-Cre;Triofl/fl mice exhibited increased bone mass due to impaired osteoclast bone resorption.
- Trio deficiency significantly suppressed osteoclast differentiation and function in vitro.
- Trio deficiency led to reduced expression of key osteoclastogenic genes and perturbed Rac1/Cdc42-PAK1-ERK/p38 signaling.
Conclusions:
- Trio is a critical regulator of osteoclast differentiation and function.
- The Trio-mediated Rac1/Cdc42-PAK1-ERK/p38 signaling pathway is essential for osteoclast bone resorption.
- Targeting Trio in osteoclasts presents a potential therapeutic avenue for bone diseases characterized by abnormal bone resorption.
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