Loss of Smad3-Mediated Negative Regulation of Runx2 Activity Leads to an Alteration in Cell Fate Determination

REFERENCES

• Alliston, T., L. Choy, P. Ducy, G. Karsenty, and R. Derynck. 2001. TGF-β-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. EMBO J. 20:2254–2272.
   PubMed Web of Science ®Google Scholar
• Bialek, P., B. Kern, X. Yang, M. Schrock, D. Sosic, N. Hong, H. Wu, K. Yu, D. M. Ornitz, E. N. Olson, M. J. Justice, and G. Karsenty. 2004. A twist code determines the onset of osteoblast differentiation. Dev. Cell 6:423–435.
   PubMed Web of Science ®Google Scholar
• Borton, A. J., J. P. Frederick, M. B. Datto, X. F. Wang, and R. S. Weinstein. 2001. The loss of Smad3 results in a lower rate of bone formation and osteopenia through dysregulation of osteoblast differentiation and apoptosis. J. Bone Miner. Res. 16:1754–1764.
   PubMedGoogle Scholar
• Bourne, G. 1972. Phosphatase and calcification., vol. 79. Academic Press, Inc., New York, N.Y.
   Google Scholar
• Choy, L., J. Skillington, and R. Derynck. 2000. Roles of autocrine TGF-β receptor and Smad signaling in adipocyte differentiation. J. Cell Biol. 149:667–682.
   PubMed Web of Science ®Google Scholar
• Datto, M. B., J. P. Frederick, L. Pan, A. J. Borton, Y. Zhuang, and X. F. Wang. 1999. Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol. Cell. Biol. 19:2495–2504.
   PubMed Web of Science ®Google Scholar
• Ducy, P. 2000. Cbfa1: a molecular switch in osteoblast biology. Dev. Dyn. 219:461–471.
   PubMed Web of Science ®Google Scholar
• Ducy, P., M. Starbuck, M. Priemel, J. Shen, G. Pinero, V. Geoffroy, M. Amling, and G. Karsenty. 1999. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev. 13:1025–1036.
   PubMed Web of Science ®Google Scholar
• Ducy, P., R. Zhang, V. Geoffroy, A. L. Ridall, and G. Karsenty. 1997. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754.
   PubMed Web of Science ®Google Scholar
• Harris, S. E., L. F. Bonewald, M. A. Harris, M. Sabatini, S. Dallas, J. Q. Feng, N. Ghosh-Choudhury, J. Wozney, and G. R. Mundy. 1994. Effects of transforming growth factor beta on bone nodule formation and expression of bone morphogenetic protein 2, osteocalcin, osteopontin, alkaline phosphatase, and type I collagen mRNA in long-term cultures of fetal rat calvarial osteoblasts. J. Bone Miner. Res. 9:855–863.
   PubMed Web of Science ®Google Scholar
• Khosla, S., and M. Kleerekoper. 1999. Biochemical markers of bone turnover, p. 128–133. In M. Favus (ed.), Primer on the metabolic bone diseases and disorders of mineral metabolism. Lippincott Williams & Wilkins, Philadelphia, Pa.
   Google Scholar
• Komori, T., H. Yagi, S. Nomura, A. Yamaguchi, K. Sasaki, K. Deguchi, Y. Shimizu, R. T. Bronson, Y. H. Gao, M. Inada, M. Sato, R. Okamoto, Y. Kitamura, S. Yoshiki, and T. Kishimoto. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764.
   PubMed Web of Science ®Google Scholar
• Liu, D., B. L. Black, and R. Derynck. 2001. TGF-β inhibits muscle differentiation through functional repression of myogenic transcription factors by Smad3. Genes Dev. 15:2950–2966.
   PubMed Web of Science ®Google Scholar
• Ma, L., S. Golden, L. Wu, and R. Maxson. 1996. The molecular basis of Boston-type craniosynostosis: the Pro148→His mutation in the N-terminal arm of the MSX2 homeodomain stabilizes DNA binding without altering nucleotide sequence preferences. Hum. Mol. Genet. 5:1915–1920.
   PubMed Web of Science ®Google Scholar
• Otto, F., A. P. Thornell, T. Crompton, A. Denzel, K. C. Gilmour, I. R. Rosewell, G. W. Stamp, R. S. Beddington, S. Mundlos, B. R. Olsen, P. B. Selby, and M. J. Owen. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89:765–771.
   PubMed Web of Science ®Google Scholar
• Roberts, A. B. 1999. TGF-β signaling from receptors to the nucleus. Microbes Infect. 1:1265–1273.
   PubMedGoogle Scholar
• Shirakabe, K., K. Terasawa, K. Miyama, H. Shibuya, and E. Nishida. 2001. Regulation of the activity of the transcription factor Runx2 by two homeobox proteins, Msx2 and Dlx5. Genes Cells 6:851–856.
   PubMed Web of Science ®Google Scholar
• Sirard, C., S. Kim, C. Mirtsos, P. Tadich, P. A. Hoodless, A. Itie, R. Maxson, J. L. Wrana, and T. W. Mak. 2000. Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor beta-related signaling. J. Biol. Chem. 275:2063–2070.
   PubMedGoogle Scholar
• Wilkie, A. O., Z. Tang, N. Elanko, S. Walsh, S. R. Twigg, J. A. Hurst, S. A. Wall, K. H. Chrzanowska, and R. E. Maxson, Jr. 2000. Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat. Genet. 24:387–390.
   PubMed Web of Science ®Google Scholar
• Willis, D. M., A. P. Loewy, N. Charlton-Kachigian, J. S. Shao, D. M. Ornitz, and D. A. Towler. 2002. Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J. Biol. Chem. 277:37280–37291.
   PubMed Web of Science ®Google Scholar
• Yingling, J. M., P. Das, C. Savage, M. Zhang, R. W. Padgett, and X. F. Wang. 1996. Mammalian dwarfins are phosphorylated in response to transforming growth factor beta and are implicated in control of cell growth. Proc. Natl. Acad. Sci. USA 93:8940–8944.
   PubMedGoogle Scholar
• Yingling, J. M., M. B. Datto, C. Wong, J. P. Frederick, N. T. Liberati, and X. F. Wang. 1997. Tumor suppressor Smad4 is a transforming growth factor beta-inducible DNA binding protein. Mol. Cell. Biol. 17:7019–7028.
   PubMed Web of Science ®Google Scholar
• Yoshizawa, T., F. Takizawa, F. Iizawa, O. Ishibashi, H. Kawashima, A. Matsuda, and N. Endo. 2004. Homeobox protein MSX2 acts as a molecular defense mechanism for preventing ossification in ligament fibroblasts. Mol. Cell. Biol. 24:3460–3472.
   PubMed Web of Science ®Google Scholar