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

BMB Rep. 2019 Jun;52(6):391-396. doi: 10.5483/BMBRep.2019.52.6.166.

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/EBPβ) has been proposed to function as a transcription factor and upregulate RANKL expression, but it is still uncertain how C/EBPβ is involved in 1,25D3-induced RANKL expression of osteoblasts. 1,25D3 stimulation increased the expression of RANKL and C/EPBβ 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/EBPβ. In contrast, C/EBPβ 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/EBPβ protein binding to the RANKL promoter. In conclusion, C/EBPβ is required for induction of RANKL by 1,25D3. [BMB Reports 2019; 52(6): 391-396].

MeSH terms

  • Binding Sites
  • CCAAT-Enhancer-Binding Protein-beta / metabolism*
  • Calcitriol / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Nucleus / metabolism
  • Humans
  • NF-kappa B / metabolism
  • Osteoblasts / cytology
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Stability
  • RANK Ligand / biosynthesis
  • RANK Ligand / genetics
  • RANK Ligand / metabolism*
  • RNA, Messenger / metabolism

Substances

  • CCAAT-Enhancer-Binding Protein-beta
  • NF-kappa B
  • RANK Ligand
  • RNA, Messenger
  • TNFSF11 protein, human
  • Calcitriol