Osteoporotic bone formation in mice lacking tob2; involvement of Tob2 in RANK ligand expression and osteoclasts differentiation.
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.
Ajima
Rieko
R
The Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Akiyama
Toru
T
Usui
Michihiko
M
Yoneda
Mitsuhiro
M
Yoshida
Yutaka
Y
Nakamura
Takahisa
T
Minowa
Osamu
O
Noda
Masaki
M
Tanaka
Sakae
S
Noda
Tetsuo
T
Yamamoto
Tadashi
T
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D017931:DNA Primers; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D010010:Osteoclasts / Q000166:cytology*; D010024:Osteoporosis / Q000235:genetics* / Q000473:pathology; D053245:RANK Ligand / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; D017931:DNA Primers; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C485732:Tob2 protein, mouse