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.