期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：17
页码：6653-6658
DOI：10.1073/pnas.0303093101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Tob (transducer of erbB2) is a member of antiproliferative family proteins and acts as a bone morphogenic protein inhibitor as well as a suppressor of proliferation in T cells, which have been implicated in postmenopausal bone loss. To determine the effect of Tob deficiency on estrogen deficiency-induced bone loss, we analyzed bone metabolism after ovariectomy or sham operation in Tob-deficient mice. Ovariectomy in WT mice decreased trabecular bone volume and bone mineral density (BMD) as expected. In Tob-deficient mice, ovariectomy reduced bone volume and BMD. However, even after ovariectomy, both trabecular bone volume and BMD levels in Tob-deficient bone were comparable to those in sham-operated WT bones. Bone formation parameters (mineral apposition rate and bone formation rate) in the ovariectomized Tob-deficient mice were significantly higher than those in the ovariectomized WT mice. In contrast, the ovariectomy-induced increase in the bone resorption parameters, osteoclast surface, and osteoclast number was similar between Tob-deficient mice and WT mice. Furthermore, in ex vivo nodule formation assay, ovariectomy-induced enhancement of nodule formation was significantly higher in the bone marrow cells from Tob-deficient mice than in the bone marrow cells from ovariectomized WT mice. Both Tob and estrogen signalings converge at bone morphogenic protein activation of alkaline phosphatase and GCCG-reporter gene expression in osteoblasts, revealing interaction between the two signals. These data indicate that Tob deficiency prevents ovariectomy-induced bone loss through the superenhancement of osteoblastic activities in bone and that this results in further augmentation in the bone formation rate and the mineral apposition rate after ovariectomy in vivo.
