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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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CCAAT/enhancer-binding protein beta (C/EBPβ) is an important mediator of 1,25 dihydroxyvitamin D3 (1,25D3)-induced receptor activator of nuclear factor kappa-B ligand (RANKL) expression in osteoblasts

  • Jo, Sungsin (Hanyang University Hospital for Rheumatic Diseases) ;
  • Lee, Yun Young (Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Hanyang University) ;
  • Han, Jinil (Hanyang University Hospital for Rheumatic Diseases) ;
  • Lee, Young Lim (Hanyang University Hospital for Rheumatic Diseases) ;
  • Yoon, Subin (Hanyang University Hospital for Rheumatic Diseases) ;
  • Lee, Jaehyun (Hanyang University Hospital for Rheumatic Diseases) ;
  • Oh, Younseo (Hanyang University Hospital for Rheumatic Diseases) ;
  • Han, Joong-Soo (Biomedical Research Institute and Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University) ;
  • Sung, Il-Hoon (Department of Orthopedic Surgery, Hanyang University Hospital) ;
  • Park, Ye-Soo (Department of Orthopedic Surgery, Hanyang University Hospital) ;
  • Kim, Tae-Hwan (Hanyang University Hospital for Rheumatic Diseases)
  • Received : 2018.07.20
  • Accepted : 2018.10.10
  • Published : 2019.06.30
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Abstract

Receptor activator of nuclear factor kappa B ligand (RANKL) expression in osteoblasts is regulated by 1,25-dihydroxyvitamin D3 (1,25D3). CCAAT/enhancer-binding protein beta ($C/EBP{\beta}$) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how $C/EBP{\beta}$ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and $C/EBP{\beta}$ genes in osteoblasts and enhanced phosphorylation and stability of these proteins. Moreover, induction of RANKL expression by 1,25D3 in osteoblasts was downregulated upon knockdown of $C/EBP{\beta}$. In contrast, $C/EBP{\beta}$ overexpression directly upregulated RANKL promoter activity and exhibited a synergistic effect on 1,25D3-induced RANKL expression. In particular, 1,25D3 treatment of osteoblasts increased $C/EBP{\beta}$ protein binding to the RANKL promoter. In conclusion, $C/EBP{\beta}$ is required for induction of RANKL by 1,25D3.

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References

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