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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
PubMed

Insights

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.
Keywords:
Bone resorptionHuman osteoclastsRabGAPTBC1D25

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