|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
Development, Vol 128, Issue 4 541-550, Copyright © 2001 by Company of Biologists
JOURNAL ARTICLES |
F Long, E Schipani, H Asahara, H Kronenberg and M Montminy
The Salk Institute for Biological Studies, Peptide Biology Laboratories, La Jolla, CA 92037, USA.
We have evaluated the importance of the CREB family of transcriptional activators for endochondral bone formation by expressing a potent dominant negative CREB inhibitor (A-CREB) in growth plate chondrocytes of transgenic mice. A-CREB transgenic mice exhibited short-limbed dwarfism and died minutes after birth, apparently due to respiratory failure from a diminished rib cage circumference. Consistent with the robust Ser133 phosphorylation and, hence, activation of CREB in chondrocytes within the proliferative zone of wild-type cartilage during development, chondrocytes in A-CREB mutant cartilage exhibited a profound decrease in proliferative index and a delay in hypertrophy. Correspondingly, the expression of certain signaling molecules in cartilage, most notably the Indian hedgehog (Ihh) receptor patched (Ptch), was lower in A-CREB expressing versus wild-type chondrocytes. CREB appears to promote Ptch expression in proliferating chondrocytes via an Ihh-independent pathway; phospho-CREB levels were comparable in cartilage from Ihh(-/-) and wild-type mice. These results demonstrate the presence of a distinct signaling pathway in developing bone that potentiates Ihh signaling and regulates chondrocyte proliferation, at least in part, via the CREB family of activators.
This article has been cited by other articles:
|
|
 |
|
  H.-S. Seo, D. D. Liu, B. N. Bekele, M.-K. Kim, K. Pisters, S. M. Lippman, I. I. Wistuba, and J. S. Koo Cyclic AMP Response Element-Binding Protein Overexpression: A Feature Associated with Negative Prognosis in Never Smokers with Non-Small Cell Lung Cancer Cancer Res., August 1, 2008; 68(15): 6065 - 6073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S.-W. Kim, J. S. Hong, S.-H. Ryu, W.-C. Chung, J.-H. Yoon, and J. S. Koo Regulation of Mucin Gene Expression by CREB via a Nonclassical Retinoic Acid Signaling Pathway Mol. Cell. Biol., October 1, 2007; 27(19): 6933 - 6947. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Huggins, J. J. Lepore, S. Greytak, R. Patten, R. McNamee, M. Aronovitz, P. J. Wang, and G. L. Reed The CREB leucine zipper regulates CREB phosphorylation, cardiomyopathy, and lethality in a transgenic model of heart failure Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1877 - H1882. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Davey and H. E. MacLean Current and future approaches using genetically modified mice in endocrine research Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E429 - E438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Matsuo, S. Tanaka, M. K. Gordon, M. Koch, H. Yoshioka, and F. Ramirez CREB-AP1 Protein Complexes Regulate Transcription of the Collagen XXIV Gene (Col24a1) in Osteoblasts J. Biol. Chem., March 3, 2006; 281(9): 5445 - 5452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Najwer and B. Lilly Ca2+/calmodulin-dependent protein kinase IV activates cysteine-rich protein 1 through adjacent CRE and CArG elements Am J Physiol Cell Physiol, October 1, 2005; 289(4): C785 - C793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Akiyama, J. P. Lyons, Y. Mori-Akiyama, X. Yang, R. Zhang, Z. Zhang, J. M. Deng, M. M. Taketo, T. Nakamura, R. R. Behringer, et al. Interactions between Sox9 and {beta}-catenin control chondrocyte differentiation Genes & Dev., May 1, 2004; 18(9): 1072 - 1087. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abramovitch, E. Tavor, J. Jacob-Hirsch, E. Zeira, N. Amariglio, O. Pappo, G. Rechavi, E. Galun, and A. Honigman A Pivotal Role of Cyclic AMP-Responsive Element Binding Protein in Tumor Progression Cancer Res., February 15, 2004; 64(4): 1338 - 1346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Harris, O. Kecha, C. Deal, C. R. Howlett, D. Deiss, V. Tobias, J. Simoneau-Roy, and J. Walker Reversible Metaphyseal Dysplasia, a Novel Bone Phenotype, in Two Unrelated Children with Autoimmunepolyendocrinopathy-Candidiasis-Ectodermal Dystrophy: Clinical and Molecular Studies J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4576 - 4585. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Terpstra, J. Prud'homme, A. Arabian, S. Takeda, G. Karsenty, S. Dedhar, and R. St-Arnaud Reduced chondrocyte proliferation and chondrodysplasia in mice lacking the integrin-linked kinase in chondrocytes J. Cell Biol., July 7, 2003; 162(1): 139 - 148. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, S. Zhuang, S. Cassenaer, D. E. Casteel, T. Gudi, G. R. Boss, and R. B. Pilz Synergism between Calcium and Cyclic GMP in Cyclic AMP Response Element-Dependent Transcriptional Regulation Requires Cooperation between CREB and C/EBP-{beta} Mol. Cell. Biol., June 15, 2003; 23(12): 4066 - 4082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Beier and P. LuValle The Cyclin D1 and Cyclin A Genes Are Targets of Activated PTH/PTHrP Receptors in Jansen's Metaphyseal Chondrodysplasia Mol. Endocrinol., September 1, 2002; 16(9): 2163 - 2173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Long, X. M. Zhang, S. Karp, Y. Yang, and A. P. McMahon Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation Development, December 15, 2001; 128(24): 5099 - 5108. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Beier, Z. Ali, D. Mok, A. C. Taylor, T. Leask, C. Albanese, R. G. Pestell, and P. LuValle TGFbeta and PTHrP Control Chondrocyte Proliferation by Activating Cyclin D1 Expression Mol. Biol. Cell, December 1, 2001; 12(12): 3852 - 3863. [Abstract] [Full Text] [PDF]
|
|
