Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Cell Biol. 172 (1): 115-125

Copyright © 2006 by the Rockefeller University Press.


p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling

Xueying Wang1, Hui-Yi Kua1, Yuanyu Hu1, Ke Guo1, Qi Zeng1, Qiang Wu2, Huck-Hui Ng2, Gerard Karsenty3, Benoit de Crombrugghe4, James Yeh5, , and Baojie Li1

1 The Institute of Molecular and Cell Biology, Singapore 138673
2 Laboratory of Cell and Medical Biology, Genome Institute of Singapore, Singapore 138672
3 Department of Molecular and Human Genetics and Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030
4 Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
5 Department of Medicine, Winthrop-University Hospital, Mineola, NY 11501

Correspondence to Baojie Li: libj{at}

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.

Abbreviations used in this paper: ALP, alkaline phosphatase; BMM, bone marrow monocyte; BMP, bone morphogenetic protein; cDNA, complementary DNA; M-CSF, macrophage-colony stimulating factor; MEF, mouse embryonic fibroblast; OPG, osteoprotegerin; RANKL, receptor activator of NF{kappa}B ligand; siRNA, small interfering RNA; TBP, thyroxine-binding protein; TRAP, tartrate-resistant acid phosphatase.

The paradigm of mutant p53-expressing cancer stem cells and drug resistance.
Y. Shetzer, H. Solomon, G. Koifman, A. Molchadsky, S. Horesh, and V. Rotter (2014)
   Abstract »    Full Text »    PDF »
MicroRNA-34c Inversely Couples the Biological Functions of the Runt-related Transcription Factor RUNX2 and the Tumor Suppressor p53 in Osteosarcoma.
M. van der Deen, H. Taipaleenmaki, Y. Zhang, N. M. Teplyuk, A. Gupta, S. Cinghu, K. Shogren, A. Maran, M. J. Yaszemski, L. Ling, et al. (2013)
J. Biol. Chem. 288, 21307-21319
   Abstract »    Full Text »    PDF »
Development of the Endochondral Skeleton.
F. Long and D. M. Ornitz (2013)
Cold Spring Harb Perspect Biol 5, a008334
   Abstract »    Full Text »    PDF »
Atypical Atm-p53 genetic interaction in osteogenesis is mediated by Smad1 signaling.
G. Ma, L. Li, Y. Hu, J. F. L. Chau, B. J. Au, D. Jia, H. Liu, J. Yeh, L. He, A. Hao, et al. (2012)
J Mol Cell Biol 4, 118-120
   Full Text »    PDF »
Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation.
M. Ishikawa, T. Iwamoto, T. Nakamura, A. Doyle, S. Fukumoto, and Y. Yamada (2011)
J. Cell Biol. 193, 1257-1274
   Abstract »    Full Text »    PDF »
Ascorbic acid regulates osterix expression in osteoblasts by activation of prolyl hydroxylase and ubiquitination-mediated proteosomal degradation pathway.
W. Xing, S. Pourteymoor, and S. Mohan (2011)
Physiol Genomics 43, 749-757
   Abstract »    Full Text »    PDF »
Extracellular Microfibrils Control Osteoblast-supported Osteoclastogenesis by Restricting TGF{beta} Stimulation of RANKL Production.
H. Nistala, S. Lee-Arteaga, S. Smaldone, G. Siciliano, and F. Ramirez (2010)
J. Biol. Chem. 285, 34126-34133
   Abstract »    Full Text »    PDF »
Fibrillin-1 and -2 differentially modulate endogenous TGF-{beta} and BMP bioavailability during bone formation.
H. Nistala, S. Lee-Arteaga, S. Smaldone, G. Siciliano, L. Carta, R. N. Ono, G. Sengle, E. Arteaga-Solis, R. Levasseur, P. Ducy, et al. (2010)
J. Cell Biol. 190, 1107-1121
   Abstract »    Full Text »    PDF »
p53 is balancing development, differentiation and de-differentiation to assure cancer prevention.
A. Molchadsky, N. Rivlin, R. Brosh, V. Rotter, and R. Sarig (2010)
Carcinogenesis 31, 1501-1508
   Abstract »    Full Text »    PDF »
p53 at a glance.
C. A. Brady and L. D. Attardi (2010)
J. Cell Sci. 123, 2527-2532
   Full Text »    PDF »
p53 Deficiency Leads to Compensatory Up-Regulation of p16INK4a.
W. F. Leong, J. F. L. Chau, and B. Li (2009)
Mol. Cancer Res. 7, 354-360
   Abstract »    Full Text »    PDF »
The Retinoblastoma Protein Tumor Suppressor Is Important for Appropriate Osteoblast Differentiation and Bone Development.
S. D. Berman, T. L. Yuan, E. S. Miller, E. Y. Lee, A. Caron, and J. A. Lees (2008)
Mol. Cancer Res. 6, 1440-1451
   Abstract »    Full Text »    PDF »
Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage.
S. D. Berman, E. Calo, A. S. Landman, P. S. Danielian, E. S. Miller, J. C. West, B. D. Fonhoue, A. Caron, R. Bronson, M. L. Bouxsein, et al. (2008)
PNAS 105, 11851-11856
   Abstract »    Full Text »    PDF »
BMP-2 Induces Osterix Expression through Up-regulation of Dlx5 and Its Phosphorylation by p38.
A. Ulsamer, Ma. J. Ortuno, S. Ruiz, A. R. G. Susperregui, N. Osses, J. L. Rosa, and F. Ventura (2008)
J. Biol. Chem. 283, 3816-3826
   Abstract »    Full Text »    PDF »
Atm-deficient mice: an osteoporosis model with defective osteoblast differentiation and increased osteoclastogenesis.
N. Rasheed, X. Wang, Q.-T. Niu, J. Yeh, and B. Li (2006)
Hum. Mol. Genet. 15, 1938-1948
   Abstract »    Full Text »    PDF »
Skeletons in the p53 tumor suppressor closet: genetic evidence that p53 blocks bone differentiation and development..
G. P. Zambetti, E. M. Horwitz, and E. Schipani (2006)
J. Cell Biol. 172, 795-797
   Abstract »    Full Text »    PDF »
p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling.
X. Wang, H.-Y. Kua, Y. Hu, K. Guo, Q. Zeng, Q. Wu, H.-H. Ng, G. Karsenty, B. de Crombrugghe, J. Yeh, et al. (2006)
J. Exp. Med. 203, i2-2
   Full Text »
Papers of Note.
Sci. Aging Knowl. Environ. 2006, nw1
   Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882