RabGAP TBC1D25 is involved in human osteoclast activity.

The osteoclast cell polarization and the ruffled border formation during bone resorption are major vesicle trafficking events. Rab GTPases have been shown to be involved in these processes, however very little is known about their regulators, such as Rab GTPase activating proteins (RabGAPs). In osteoclasts, we previously identified two spliced isoforms of TBC1D25, encoding a RabGAP which had never been studied in these cells. Using in vitro cultures, we evaluated the expression of TBC1D25 in human osteoclasts. TBC1D25 was expressed at the sealing zone co-localizing with F-actin, with an annular distribution, and also at the ruffled membrane with a less intense colocalization with LAMP2 and cathepsin K, but none with Rab7 or V-ATPase. Inhibiting TBC1D25 expression significantly decreased bone resorption, as well as the formation of multinucleated cells and the number of nuclei per cell. These results suggest that TBC1D25 has a role in bone resorption via the regulation of osteoclast polarization and resorption, and multinucleation as well.