Exp Mol Med.  2015 Dec;47(12):e199. 10.1038/emm.2015.94.

Adseverin mediates RANKL-induced osteoclastogenesis by regulating NFATc1

• Song MK
• Lee ZH
• Kim HH

• KMID: 2359886
• DOI: http://doi.org/10.1038/emm.2015.94

Abstract

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.

MeSH Terms

Active Transport, Cell Nucleus
Animals
Bone Resorption/genetics/metabolism/pathology
Cell Differentiation
Cells, Cultured
Female
Gelsolin/genetics/*metabolism
Gene Knockdown Techniques
Humans
Mice, Inbred ICR
NF-kappa B/metabolism
NFATC Transcription Factors/*metabolism
Osteoclasts/*cytology/metabolism/pathology
RANK Ligand/*metabolism
Gelsolin
NF-kappa B
NFATC Transcription Factors
RANK Ligand