Adseverin is a Ca2+-dependent
actin filament-severing
protein that has been reported to regulate
exocytosis via rearrangements of the
actin cytoskeleton in secretory
cells. However, the
role of adseverin in
bone cells has not yet been well characterized. Here, we investigated the
role of adseverin in
osteoclastogenesis using primary
osteoclast precursor
cells. Adseverin expression was upregulated during RANKL (
receptor activator of nuclear factor-kappaB ligand)-induced
osteoclast differentiation. Moreover, genetic silencing of adseverin decreased the number of
osteoclasts generated by RANKL. Adseverin knockdown also suppressed the RANKL-mediated induction of nuclear factor of activated
T-cell c1 (NFATc1), which is a key
transcription factor in
osteoclastogenesis. In addition, adseverin knockdown impaired
bone resorption and the
secretion of
bone-degrading
enzymes from
osteoclasts. These effects were accompanied by decreased NFATc1 expression and the activation of
nuclear factor-kappaB. Collectively, our results indicate that adseverin has a crucial
role in
osteoclastogenesis by regulating NFATc1.