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

Edited by Jesus Avila

Received 24 December 2007; received in revised form 8 March 2008; accepted 11 March 2008. published online 19 March 2008.

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 D3-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 D3 receptor (VDR), which suggests its involvement in vitamin D3 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.

Abbreviations: RANKL, receptor activator of NF-κB ligand, FBS, fetal bovine serum, RT-PCR, reverse-transcriptase polymerase chain reaction, MEFs, mouse embryonic fibroblasts, TRAP, tartrate-resistant acid phosphatase, GST, glutathione-s-transferase

Keywords: Bone mass, Osteoclast, Gene targeting, tob Family, Vitamin D3

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

b Faculty of Medicine, University of Tokyo, Tokyo, Japan

c Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan

d Showa University School of Dentistry, Tokyo, Japan

e Cancer Institute, Tokyo, Japan

Corresponding author. Fax: +81 3 5449 5413.

PII: S0014-5793(08)00241-X

doi:10.1016/j.febslet.2008.03.012

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