title: Adseverin mediates RANKL-induced osteoclastogenesis by regulating NFATc1.
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-κB 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-κB. Collectively, our results indicate that adseverin has a crucial role in osteoclastogenesis by regulating NFATc1.
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Song
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Zang Hee
authors.initials: ZH
authors.lastname: Lee
authors.affiliation: Department of Cell and Developmental Biology, BK21 Program and Dental Research Institute, Seoul National University School of Dentistry, Seoul, Korea.
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Kim
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D018260:Gelsolin / Q000235:genetics / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000378:metabolism*
chemical_list: D018260:Gelsolin; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; C065395:scinderin