Downregulation of Runx2 by 1,25-Dihydroxyvitamin D₃ Induces the Transdifferentiation of Osteoblasts to Adipocytes

Int J Mol Sci. 2016 May 19;17(5):770. doi: 10.3390/ijms17050770.

Abstract

1,25-Dihydroxyvitamin D₃ (1,25(OH)₂D₃) indirectly stimulates bone formation, but little is known about its direct effect on bone formation. In this study, we observed that 1,25(OH)₂D₃ enhances adipocyte differentiation, but inhibits osteoblast differentiation during osteogenesis. The positive role of 1,25(OH)₂D₃ in adipocyte differentiation was confirmed when murine osteoblasts were cultured in adipogenic medium. Additionally, 1,25(OH)₂D₃ enhanced the expression of adipocyte marker genes, but inhibited the expression of osteoblast marker genes in osteoblasts. The inhibition of osteoblast differentiation and promotion of adipocyte differentiation mediated by 1,25(OH)₂D₃ were compensated by Runx2 overexpression. Our results suggest that 1,25(OH)₂D₃ induces the transdifferentiation of osteoblasts to adipocytes via Runx2 downregulation in osteoblasts.

Keywords: 1,25(OH)2D3; adipocyte; osteoblast; transdifferentiation.

MeSH terms

  • Adipocytes / cytology
  • Adipocytes / metabolism*
  • Animals
  • Calcitriol / pharmacology*
  • Cell Transdifferentiation / drug effects*
  • Core Binding Factor Alpha 1 Subunit / biosynthesis*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Down-Regulation / drug effects*
  • Mice
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Runx2 protein, mouse
  • Calcitriol