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

Rieko Ajima1, Toru Akiyama, Michihiko Usui

  • 1The Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

FEBS Letters
|March 25, 2008
PubMed

Insights

The antiproliferative gene Tob2 negatively regulates bone loss by suppressing osteoclast formation. Tob2 interacts with the vitamin D receptor to control RANKL expression, impacting bone mass.

Area of Science:

  • Bone Biology
  • Cellular and Molecular Biology
  • Gene Regulation

Background:

  • Tob2 is a member of the antiproliferative gene family.
  • Osteoclasts play a critical role in bone resorption and bone mass regulation.
  • Vitamin D receptor (VDR) signaling influences bone metabolism, including osteoclastogenesis.

Purpose of the Study:

  • To investigate the role of Tob2 in bone metabolism and osteoclast formation.
  • To elucidate the molecular mechanism by which Tob2 regulates osteoclastogenesis.
  • To determine the interaction between Tob2 and the vitamin D receptor (VDR) in regulating RANKL expression.

Main Methods:

  • Analysis of bone mass and osteoclast number in mice lacking Tob2.
  • Overexpression of Tob2 in stromal cells to assess its effect on osteoclast formation.
  • Measurement of RANKL mRNA expression in stromal cells under different Tob2 conditions.
  • Investigation of the interaction between Tob2 and VDR using co-immunoprecipitation or similar techniques.

Main Results:

  • Mice lacking Tob2 exhibited decreased bone mass and increased osteoclast numbers.
  • Overexpression of Tob2 in stromal cells suppressed vitamin D(3)-induced osteoclast formation.
  • RANKL mRNA expression was elevated in Tob2-deficient stromal cells and reduced when Tob2 was present.
  • Tob2 was found to interact with the vitamin D receptor (VDR).

Conclusions:

  • Tob2 negatively regulates osteoclast formation, thereby influencing bone mass.
  • Tob2 suppresses RANKL expression through its interaction with VDR.
  • This interaction suggests Tob2 is involved in VDR-mediated transcriptional regulation impacting bone homeostasis.

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