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Tusc2/Fus1 regulates osteoclast differentiation through NF-κB and NFATc1

  • Kim, Inyoung (Department of Pharmacology, Chonnam National University Medical School) ;
  • Kim, Jung Ha (Department of Pharmacology, Chonnam National University Medical School) ;
  • Kim, Kabsun (Department of Pharmacology, Chonnam National University Medical School) ;
  • Seong, Semun (Department of Pharmacology, Chonnam National University Medical School) ;
  • Kim, Nacksung (Department of Pharmacology, Chonnam National University Medical School)
  • Received : 2017.02.18
  • Accepted : 2017.04.03
  • Published : 2017.09.30

Abstract

Tumor suppressor candidate 2 (Tusc2, also known as Fus1) regulates calcium signaling, and $Ca^{2+}$-dependent nuclear factor of activated T-cells (NFAT) and nuclear factor kappa B ($NF-{\kappa}B$) pathways, which play roles in osteoclast differentiation. However, the role of Tusc2 in osteoclasts remains unknown. Here, we report that Tusc2 positively regulates the differentiation of osteoclasts. Overexpression of Tusc2 in osteoclast precursor cells enhanced receptor activator of nuclear factor ${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. In contrast, small interfering RNA-mediated knockdown of Tusc2 strongly inhibited osteoclast differentiation. In addition, Tusc2 induced the activation of RANKL-mediated $NF-{\kappa}B$ and calcium/calmodulin-dependent kinase IV (CaMKIV)/cAMP-response element (CRE)-binding protein CREB signaling cascades. Taken together, these results suggest that Tusc2 acts as a positive regulator of RANKL-mediated osteoclast differentiation.

Keywords

References

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