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Science 16 December 1988:
Vol. 242. no. 4885, pp. 1528 - 1534
DOI: 10.1126/science.3201241
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Articles

Science, Vol 242, Issue 4885, 1528-1534
Copyright © 1988 by American Association for the Advancement of Science

articles

Novel regulators of bone formation: molecular clones and activities

JM Wozney, V Rosen, AJ Celeste, LM Mitsock, MJ Whitters, RW Kriz, RM Hewick, and EA Wang

Tissue Growth and Repair Program, Genetics Institute, Inc., Cambridge, MA 02140.

Protein extracts derived from bone can initiate the process that begins with cartilage formation and ends in de novo bone formation. The critical components of this extract, termed bone morphogenetic protein (BMP), that direct cartilage and bone formation as well as the constitutive elements supplied by the animal during this process have long remained unclear. Amino acid sequence has been derived from a highly purified preparation of BMP from bovine bone. Now, human complementary DNA clones corresponding to three polypeptides present in this BMP preparation have been isolated, and expression of the recombinant human proteins have been obtained. Each of the three (BMP-1, BMP-2A, and BMP-3) appears to be independently capable of inducing the formation of cartilage in vivo. Two of the encoded proteins (BMP-2A and BMP-3) are new members of the TGF-beta supergene family, while the third, BMP-1, appears to be a novel regulatory molecule.


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Expression of Bone Morphogenetic Proteins in Human Lung Carcinomas.
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Transient Changes in Oxygen Tension Inhibit Osteogenic Differentiation and Runx2 Expression in Osteoblasts.
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J. Biol. Chem. 279, 40007-40016
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Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification.
T. M. Doherty, L. A. Fitzpatrick, D. Inoue, J.-H. Qiao, M. C. Fishbein, R. C. Detrano, P. K. Shah, and T. B. Rajavashisth (2004)
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J. Biol. Chem. 279, 15916-15928
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M. Zhao, M. Qiao, S. E. Harris, B. O. Oyajobi, G. R. Mundy, and D. Chen (2004)
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Bone Morphogenetic Protein-2 Stimulates Angiogenesis in Developing Tumors.
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C. A. Luppen, N. Leclerc, T. Noh, A. Barski, A. Khokhar, A. L. Boskey, E. Smith, and B. Frenkel (2003)
J. Biol. Chem. 278, 44995-45003
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Sulfated Polysaccharides Enhance the Biological Activities of Bone Morphogenetic Proteins.
T. Takada, T. Katagiri, M. Ifuku, N. Morimura, M. Kobayashi, K. Hasegawa, A. Ogamo, and R. Kamijo (2003)
J. Biol. Chem. 278, 43229-43235
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The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells.
E. M. Langenfeld, S. E. Calvano, F. Abou-Nukta, S. F. Lowry, P. Amenta, and J. Langenfeld (2003)
Carcinogenesis 24, 1445-1454
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A Single Percutaneous Injection of Recombinant Human Bone Morphogenetic Protein-2 Accelerates Fracture Repair.
T. A. Einhorn, R. J Majeska, A. Mohaideen, E. M. Kagel, M. L. Bouxsein, T. J. Turek, and J. M. Wozney (2003)
J. Bone Joint Surg. Am. 85, 1425-1435
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Osteogenic Activity of the Fourteen Types of Human Bone Morphogenetic Proteins (BMPs).
H. Cheng, W. Jiang, F. M. Phillips, R. C. Haydon, Y. Peng, L. Zhou, H. H. Luu, N. An, B. Breyer, P. Vanichakarn, et al. (2003)
J. Bone Joint Surg. Am. 85, 1544-1552
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Marshall R. Urist: A Renaissance Scientist and Orthopaedic Surgeon.
A. H. Reddi (2003)
J. Bone Joint Surg. Am. 85, 3-7
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Signal Transduction of Bone Morphogenetic Proteins in Osteoblast Differentiation.
P. t. Dijke, J. Fu, P. Schaap, and B. A.J. Roelen (2003)
J. Bone Joint Surg. Am. 85, 34-38
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Clinical Applications of Recombinant Human BMPs: Early Experience and Future Development.
T. A. Einhorn (2003)
J. Bone Joint Surg. Am. 85, 82-88
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Use of Bmp1/Tll1 Doubly Homozygous Null Mice and Proteomics To Identify and Validate In Vi