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

J. Cell Biol., 2 January 2006
Vol. 172, Issue 1, p. 115-125
DOI: 10.1083/jcb.200507106

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

  1. Xueying Wang 1 ,
  2. Hui-Yi Kua 1 ,
  3. Yuanyu Hu 1 ,
  4. Ke Guo 1 ,
  5. Qi Zeng 1 ,
  6. Qiang Wu 2 ,
  7. Huck-Hui Ng 2 ,
  8. Gerard Karsenty 3 ,
  9. Benoit de Crombrugghe 4 ,
  10. James Yeh 5 , and
  11. Baojie Li 1
  1. 1The Institute of Molecular and Cell Biology, Singapore 138673
  2. 2Laboratory of Cell and Medical Biology, Genome Institute of Singapore, Singapore 138672
  3. 3Department of Molecular and Human Genetics and Bone Disease Program of Texas, Baylor College of Medicine, Houston, TX 77030
  4. 4Department of Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030
  5. 5Department of Medicine, Winthrop-University Hospital, Mineola, NY 11501
  1. Correspondence to Baojie Li: libj{at}imcb.a-star.edu.sg

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.

Footnotes

  • 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 NFκB ligand; siRNA, small interfering RNA; TBP, thyroxine-binding protein; TRAP, tartrate-resistant acid phosphatase.

    • Submitted: 21 July 2005
    • Accepted: 22 November 2005

Citation:

X. Wang, H.-Y. Kua, Y. Hu, K. Guo, Q. Zeng, Q. Wu, H.-H. Ng, G. Karsenty, B. de Crombrugghe, J. Yeh, and B. Li, p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling. J. Cell Biol. 172, 115-125 (2006).

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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.
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Papers of Note
H.-Y. Kua, Y. Hu, K. Guo, Q. Zeng, Q. Wu, H.-H. Ng, G. Karsenty, B. de Crombrugghe, J. Yeh, B. Li et al.
SAGE KE 2006, nw1-nw1 (4 January 2006)

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