Enhancing effect of Tob deficiency on bone formation is specific to bone morphogenetic protein-induced osteogenesis.
Tob is a recently reported novel bone morphogenetic protein (BMP) inhibitor, which originally was identified by West-Western procedure using ErbB2 as a probe and contains a nuclear localization signal. To further characterize the effects of Tob deficiency on BMP-induced new bone (NB) formation, we examined microcomputed tomography (microCT) on the cross-section of the bone induced by daily injection with BMP onto the calvariae of newborn mice. The calvariae of the saline-injected Tob-deficient (TD) mice were similar to those of the saline-injected or untreated wild-type (WT) mice. BMP injection locally produced NB on the calvaria in WT mice as known previously. In contrast to WT mice, BMP injection onto the calvariae of TD mice produced a calcified area in the cross-section of NB, which was more than that produced by BMP in the WT calvariae. In addition, the horizontal width and the vertical height of the NB induced by BMP in TD mice were several-fold more than those in WT mice. The effect of Tob deficiency on bone-forming activity was selective to the response to the injection with BMP because the levels of injury-induced NB formation examined by microCT 10 days after bone marrow ablation in the femora were similar between the TD and WT mice. These data indicate that Tob acts as a novel specific antagonist against bone formation induced by BMP treatment in bone.
Usui
Michihiko
M
Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Yoshida
Yutaka
Y
Yamashita
Teruhito
T
Tsuji
Kunikazu
K
Isao
Ishikawa
I
Yamamoto
Tadashi
T
Nifuji
Akira
A
Noda
Masaki
M
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D010012:Osteogenesis / Q000502:physiology*; D014057:Tomography, X-Ray Computed
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C490903:Tob1 protein, mouse