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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Actin-binding LIM protein 1 regulates receptor activator of NF-κB ligand-mediated osteoclast differentiation and motility

  • Jin, Su Hyun (Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine) ;
  • Kim, Hyunsoo (Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine) ;
  • Gu, Dong Ryun (Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine) ;
  • Park, Keun Ha (Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine) ;
  • Lee, Young Rae (Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine) ;
  • Choi, Yongwon (Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine) ;
  • Lee, Seoung Hoon (Center for Metabolic Function Regulation (CMFR), Wonkwang University School of Medicine)
  • Received : 2018.05.11
  • Accepted : 2018.05.29
  • Published : 2018.07.31
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Abstract

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of $NF-{\kappa}B$ ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

Keywords

References

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