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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.
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참고문헌 (24)
참고문헌 신청
Asagiri M / 2005 / Autoamplification of NFATc1 expression determines its essential role in bone homeostasis / J Exp Med 202 : 1261 ~ 1269
Chellaiah M / 2000 / Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength / J Cell Biol 148 : 665 ~ 678
Chumnarnsilpa S / 2009 / The crystal structure of the C-terminus of adseverin reveals the actin-binding interface / Proc Natl Acad Sci USA 106 : 13719 ~ 13724
Cremasco V / 2012 / Protein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts
Doyle SL / 2005 / Bruton’s tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536during NFkappaB activation by lipopolysacchar
Chellaiah M / 2000 / Gelsolin deficiency blocks podosome assembly and produces increased bone mass and strength / J Cell Biol 148 : 665 ~ 678
Chumnarnsilpa S / 2009 / The crystal structure of the C-terminus of adseverin reveals the actin-binding interface / Proc Natl Acad Sci USA 106 : 13719 ~ 13724
Cremasco V / 2012 / Protein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts
Doyle SL / 2005 / Bruton’s tyrosine kinase is involved in p65-mediated transactivation and phosphorylation of p65 on serine 536during NFkappaB activation by lipopolysacchar
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