- Paper Report
- Open Access
Negative regulation of BMP signaling by Tob
- Riako Masuda1
© Biomed Central Ltd 2001
- Published: 23 February 2001
The mechanisms of bone remodeling have been studied for years, but the molecular control of osteoblast differentiation and function is much less understood than that of osteoclasts because no adequate murine models exist. The aim of this study was to analyze the role of tob in osteoblast proliferation and differentiation by generatig tob-/- mice.
Tob protein interacts with the ERBB2 gene product p185; its amino terminus is homologous to the antiproliferative gene product BTG1. Overexpressed Tob has been shown to suppress the growth of NIH3T3 cells. The expression of tobhas been observed in various cells, but this is the first about expression in osteoblasts.
The tob-/- mice showed an increased bone mass due to increased numbers of osteoblasts, with no changes in the number and function of osteoclasts. Bone morphogenetic protein (BMP)-2 induced osteoblast maturation, and bone formation was enhanced in tob-/- mice. Furthermore, Tob repressed, but BMP induced, Smad-dependent transcription by ligand-dependent association with R-Smads (Smads 1, 5, and 8). The authors suggest that Tob plays a critical role as a Smad inhibitor in BMP-2/Smad-regulated gene expression in osteoblasts.
Tob-deficient mice, transient transfection, reporter gene assays, immunoprecipitation, immunofluorescence