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RabGAP TBC1D25 is involved in human osteoclast activity.
Michèle Roy1, Elizabeth Stephens1, Sophie Bouhour1
1Division of Rheumatology, Department of Medicine, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, PQ, Canada.
European Journal of Cell Biology
|December 23, 2020
Summary
This study reveals that TBC1D25, a Rab GTPase activating protein (RabGAP), is crucial for osteoclast function. Inhibiting TBC1D25 significantly impairs bone resorption and cell multinucleation.
Area of Science:
- Cell Biology
- Bone Biology
- Molecular Biology
Background:
- Osteoclast polarization and ruffled border formation are key to bone resorption, involving vesicle trafficking.
- Rab GTPases regulate these processes, but their regulators, like Rab GTPase activating proteins (RabGAPs), are poorly understood in osteoclasts.
- Two TBC1D25 RabGAP isoforms were previously identified in osteoclasts, with their specific roles unelucidated.
Purpose of the Study:
- To investigate the expression and function of TBC1D25 in human osteoclasts.
- To determine the role of TBC1D25 in osteoclast polarization, bone resorption, and multinucleation.
Main Methods:
- In vitro cultures of human osteoclasts were used.
- TBC1D25 expression and localization were analyzed using immunofluorescence, co-localizing with F-actin, LAMP2, and cathepsin K.
- The effect of TBC1D25 inhibition on bone resorption, cell formation, and nuclearity was assessed.
Main Results:
- TBC1D25 was expressed in human osteoclasts, localizing to the sealing zone with F-actin and the ruffled membrane with LAMP2 and cathepsin K.
- Inhibition of TBC1D25 significantly reduced bone resorption activity.
- TBC1D25 inhibition also decreased the formation of multinucleated cells and the number of nuclei per cell.
Conclusions:
- TBC1D25 plays a significant role in regulating osteoclast polarization and bone resorption.
- TBC1D25 is implicated in the multinucleation process of osteoclasts.
- TBC1D25 represents a potential therapeutic target for modulating bone resorption.
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