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p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling
Abstract
p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast differentiation, bone formation, and osteoblast-dependent osteoclast differentiation. Indeed, p53−/− mice display a high bone mass phenotype, and p53−/− osteoblasts show accelerated differentiation, secondary to an increase in expression of the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that p53 represses osterix transcription by the minimal promoter in a DNA-binding–independent manner. In addition, p53−/− osteoblasts have an enhanced ability to favor osteoclast differentiation, in association with an increase in expression of macrophage-colony stimulating factor, which is under the control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus, these results identify p53 as a novel regulator of osteoblast differentiation, osteoblast-dependent osteoclastogenesis, and bone remodeling.
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“In contrast to these scenarios, p53 can also suppress differentiation, as exemplified by its ability to inhibit osteoblast differentiation and bone development in mice (Lengner et al., 2006; Wang et al., 2006).”
From p53 at a glance (2010) · cites this paper as Wang et al., 2006
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Osteoclast differentiation and activation
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Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours
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Metadata
- Authors
- Wang, X., Kua, H.-Y., Hu, Y., Guo, K., Zeng, Q., Wu, Q., Ng, H.-H., Karsenty, G., de Crombrugghe, B., Yeh, J., & Li, B.
- Affiliations
- 1The Institute of Molecular and Cell Biology, Singapore 138673
- 2Laboratory of Cell and Medical Biology, Genome Institute of Singapore, Singapore 138672
- 3Department of Molecular and Human Genetics and Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030
- 4Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
- 5Department of Medicine, Winthrop-University Hospital, Mineola, NY 11501
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-12-27
- Volume
- 172
- Issue
- 1
- Pages
- 115-125
- ISSN
- 1540-8140
- 0021-9525
- Cited by
- 225
- References
- 8
- Language
- en
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