Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation

FEBS Lett. 2008 Apr 16;582(9):1313-8. doi: 10.1016/j.febslet.2008.03.012. Epub 2008 Mar 20.

Abstract

Mice lacking tob2, a member of the antiproliferative family genes, had decreased bone mass, and the number of osteoclasts differentiated from bone marrow cells was increased. Overexpression of Tob2 in stromal cells repressed vitamin D(3)-induced osteoclasts formation. Furthermore, expression of RANKL mRNA in stromal cells was increased in the absence of Tob2 and decreased in the presence of Tob2. Tob2 interacted with vitamin D(3) receptor (VDR), which suggests its involvement in vitamin D(3) receptor-mediated regulation of transcription. Because VDR regulates RANKL expression, our data suggest that Tob2 negatively regulates formation of osteoclasts by suppressing RANKL expression through its interaction with VDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Differentiation*
  • Chlorocebus aethiops
  • DNA Primers
  • Mice
  • Mice, Inbred C57BL
  • Organ Size
  • Osteoclasts / cytology*
  • Osteoporosis / genetics*
  • Osteoporosis / pathology
  • RANK Ligand / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cell Cycle Proteins
  • DNA Primers
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Tob2 protein, mouse