| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655 [J. P., M. G., S. K. Z., D. V., J. L. S., J. B. L., G. S. S., A. J. v. W.]; Bone Metabolism/Osteoporosis, Women’s Health Research Institute, Wyeth Research, Collegeville, Pennsylvania 19426 [B. M. B., J. A. R.]; Department of Biochemistry, Kyungpook National University, Daegu, Republic of Korea 700-422 [J-Y. C.]; and Department of Molecular Medicine, Osaka University Medical School, Osaka, Japan 565-0871 [T. K.]
The Runx2 (CBFA1/AML3/PEBP2
A) transcription factor promotes lineage commitment and differentiation by activating bone phenotypic genes in postproliferative osteoblasts. However, the presence of Runx2 in actively dividing osteoprogenitor cells suggests that the protein may also participate in control of osteoblast growth. Here, we show that Runx2 is stringently regulated with respect to cell cycle entry and exit in osteoblasts. We addressed directly the contribution of Runx2 to bone cell proliferation using calvarial osteoblasts from wild-type and Runx2-deficient mice (i.e., Runx2-/- and Runx2
C/C). Runx2C/C mice express a protein lacking the Runx2 COOH terminus, which integrates several cell proliferation-related signaling pathways (e.g., Smad, Yes/Src, mitogen-activated protein kinase, and retinoblastoma protein). Calvarial cells but not embryonic fibroblasts from Runx2-/- or Runx2C/C mutant mice exhibit increased cell growth rates as reflected by elevations of DNA synthesis and G1-S phase markers (e.g., cyclin E). Reintroduction of Runx2 into Runx2-/- calvarial cells by adenoviral delivery restores stringent cell growth control. Thus, Runx2 regulates normal osteoblast proliferation, and the COOH-terminal region is required for this biological function. We propose that Runx2 promotes osteoblast maturation at a key developmental transition by supporting exit from the cell cycle and activating genes that facilitate bone cell phenotype development.
This article has been cited by other articles:
|
|
 |
|
  N. M. Teplyuk, Y. Zhang, Y. Lou, J. R. Hawse, M. Q. Hassan, V. I. Teplyuk, J. Pratap, M. Galindo, J. L. Stein, G. S. Stein, et al. The Osteogenic Transcription Factor Runx2 Controls Genes Involved in Sterol/Steroid Metabolism, Including Cyp11a1 in Osteoblasts Mol. Endocrinol., June 1, 2009; 23(6): 849 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Miraoui, K. Oudina, H. Petite, Y. Tanimoto, K. Moriyama, and P. J. Marie Fibroblast Growth Factor Receptor 2 Promotes Osteogenic Differentiation in Mesenchymal Cells via ERK1/2 and Protein Kinase C Signaling J. Biol. Chem., February 20, 2009; 284(8): 4897 - 4904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lou, A. Javed, S. Hussain, J. Colby, D. Frederick, J. Pratap, R. Xie, T. Gaur, A. J. van Wijnen, S. N. Jones, et al. A Runx2 threshold for the cleidocranial dysplasia phenotype Hum. Mol. Genet., February 1, 2009; 18(3): 556 - 568. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bakshi, S. K. Zaidi, S. Pande, M. Q. Hassan, D. W. Young, M. Montecino, J. B. Lian, A. J. van Wijnen, J. L. Stein, and G. S. Stein The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes J. Cell Sci., December 1, 2008; 121(23): 3981 - 3990. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Teplyuk, M. Galindo, V. I. Teplyuk, J. Pratap, D. W. Young, D. Lapointe, A. Javed, J. L. Stein, J. B. Lian, G. S. Stein, et al. Runx2 Regulates G Protein-coupled Signaling Pathways to Control Growth of Osteoblast Progenitors J. Biol. Chem., October 10, 2008; 283(41): 27585 - 27597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. I. Aqeilan, M. Q. Hassan, A. de Bruin, J. P. Hagan, S. Volinia, T. Palumbo, S. Hussain, S.-H. Lee, T. Gaur, G. S. Stein, et al. The WWOX Tumor Suppressor Is Essential for Postnatal Survival and Normal Bone Metabolism J. Biol. Chem., August 1, 2008; 283(31): 21629 - 21639. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Zaidi, S. Pande, J. Pratap, T. Gaur, S. Grigoriu, S. A. Ali, J. L. Stein, J. B. Lian, A. J. van Wijnen, and G. S. Stein Runx2 deficiency and defective subnuclear targeting bypass senescence to promote immortalization and tumorigenic potential PNAS, December 11, 2007; 104(50): 19861 - 19866. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kilbey, K. Blyth, S. Wotton, A. Terry, A. Jenkins, M. Bell, L. Hanlon, E. R. Cameron, and J. C. Neil Runx2 Disruption Promotes Immortalization and Confers Resistance to Oncogene-Induced Senescence in Primary Murine Fibroblasts Cancer Res., December 1, 2007; 67(23): 11263 - 11271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Manton, D. F. M. Leong, S. M. Cool, and V. Nurcombe Disruption of Heparan and Chondroitin Sulfate Signaling Enhances Mesenchymal Stem Cell-Derived Osteogenic Differentiation via Bone Morphogenetic Protein Signaling Pathways Stem Cells, November 1, 2007; 25(11): 2845 - 2854. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Merciris, C. Marty, C. Collet, M.-C. de Vernejoul, and V. Geoffroy Overexpression of the Transcriptional Factor Runx2 in Osteoblasts Abolishes the Anabolic Effect of Parathyroid Hormone in Vivo Am. J. Pathol., May 1, 2007; 170(5): 1676 - 1685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. W. Young, M. Q. Hassan, X.-Q. Yang, M. Galindo, A. Javed, S. K. Zaidi, P. Furcinitti, D. Lapointe, M. Montecino, J. B. Lian, et al. Mitotic retention of gene expression patterns by the cell fate-determining transcription factor Runx2 PNAS, February 27, 2007; 104(9): 3189 - 3194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Q. Hassan, R. S. Tare, S. H. Lee, M. Mandeville, M. I. Morasso, A. Javed, A. J. van Wijnen, J. L. Stein, G. S. Stein, and J. B. Lian BMP2 Commitment to the Osteogenic Lineage Involves Activation of Runx2 by DLX3 and a Homeodomain Transcriptional Network J. Biol. Chem., December 29, 2006; 281(52): 40515 - 40526. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Guenou, K. Kaabeche, C. Dufour, H. Miraoui, and P. J. Marie Down-Regulation of Ubiquitin Ligase Cbl Induced by Twist Haploinsufficiency in Saethre-Chotzen Syndrome Results in Increased PI3K/Akt Signaling and Osteoblast Proliferation Am. J. Pathol., October 1, 2006; 169(4): 1303 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Zaragoza, E. Lopez-Rivera, C. Garcia-Rama, M. Saura, A. Martinez-Ruiz, T. R. Lizarbe, F. Martin-de-Lara, and S. Lamas Cbfa-1 mediates nitric oxide regulation of MMP-13 in osteoblasts. J. Cell Sci., May 1, 2006; 119(Pt 9): 1896 - 1902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Qiao, P. Shapiro, M. Fosbrink, H. Rus, R. Kumar, and A. Passaniti Cell Cycle-dependent Phosphorylation of the RUNX2 Transcription Factor by cdc2 Regulates Endothelial Cell Proliferation J. Biol. Chem., March 17, 2006; 281(11): 7118 - 7128. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Blyth, F. Vaillant, L. Hanlon, N. Mackay, M. Bell, A. Jenkins, J. C. Neil, and E. R. Cameron Runx2 and MYC Collaborate in Lymphoma Development by Suppressing Apoptotic and Growth Arrest Pathways In vivo Cancer Res., February 15, 2006; 66(4): 2195 - 2201. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pratap, A. Javed, L. R. Languino, A. J. van Wijnen, J. L. Stein, G. S. Stein, and J. B. Lian The Runx2 Osteogenic Transcription Factor Regulates Matrix Metalloproteinase 9 in Bone Metastatic Cancer Cells and Controls Cell Invasion Mol. Cell. Biol., October 1, 2005; 25(19): 8581 - 8591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Galindo, J. Pratap, D. W. Young, H. Hovhannisyan, H.-J. Im, J.-Y. Choi, J. B. Lian, J. L. Stein, G. S. Stein, and A. J. van Wijnen The Bone-specific Expression of Runx2 Oscillates during the Cell Cycle to Support a G1-related Antiproliferative Function in Osteoblasts J. Biol. Chem., May 27, 2005; 280(21): 20274 - 20285. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schmidt, T. Schinke, M. Haberland, M. Priemel, A. F. Schilling, C. Mueldner, J. M. Rueger, E. Sock, M. Wegner, and M. Amling The high mobility group transcription factor Sox8 is a negative regulator of osteoblast differentiation J. Cell Biol., March 14, 2005; 168(6): 899 - 910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V B Andela, F Siddiqui, A Groman, and R N Rosier An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NF{kappa}B in human osteosarcoma J. Clin. Pathol., March 1, 2005; 58(3): 328 - 330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Javed, G. L. Barnes, J. Pratap, T. Antkowiak, L. C. Gerstenfeld, A. J. van Wijnen, J. L. Stein, J. B. Lian, and G. S. Stein Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo PNAS, February 1, 2005; 102(5): 1454 - 1459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Thomas, S. A. Johnson, N. A. Sims, M. K. Trivett, J. L. Slavin, B. P. Rubin, P. Waring, G. A. McArthur, C. R. Walkley, A. J. Holloway, et al. Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma J. Cell Biol., December 6, 2004; 167(5): 925 - 934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Barnes, K. E. Hebert, M. Kamal, A. Javed, T. A. Einhorn, J. B. Lian, G. S. Stein, and L. C. Gerstenfeld Fidelity of Runx2 Activity in Breast Cancer Cells Is Required for the Generation of Metastases-Associated Osteolytic Disease Cancer Res., July 1, 2004; 64(13): 4506 - 4513. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
