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

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