Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 649K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Zhao, M. Articles by Di Chen Search for Related Content PubMed PubMed Citation Articles by Zhao, M. Articles by Di Chen, Social Bookmarking                            What's this?

© The Rockefeller University Press, 0021-9525/2002/6/1049 $5.00
The Journal of Cell Biology, Volume 157, Number 6, June 10, 2002 1049-1060

Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation

¹ Department of Medicine, Division of Endocrinology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229
² Department of Medicine, University of Kentucky, Lexington, KY 40536
³ Department of Biochemistry, Faculty of Dentistry, Osaka University, Osaka 565-0871, Japan

Address correspondence to Di Chen, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., Mail code 7877, San Antonio, TX 78229-3900. Tel.: (210) 614-0770 Ext. 239. Fax: (210) 614-0797. E-mail: chend1{at}uthscsa.edu

Functions of bone morphogenetic proteins (BMPs) are initiated by signaling through specific type I and type II serine/threonine kinase receptors. In previous studies, we have demonstrated that the type IB BMP receptor (BMPR-IB) plays an essential and specific role in osteoblast commitment and differentiation. To determine the role of BMP receptor signaling in bone formation in vivo, we generated transgenic mice, which express a truncated dominant-negative BMPR-IB targeted to osteoblasts using the type I collagen promoter. The mice are viable and fertile. Tissue-specific expression of the truncated BMPR-IB was demonstrated. Characterization of the phenotype of these transgenic mice showed impairment of postnatal bone formation in 1-mo-old homozygous transgenic mice. Bone mineral density, bone volume, and bone formation rates were severely reduced, but osteoblast and osteoclast numbers were not significantly changed in the transgenic mice. To determine whether osteoblast differentiation is impaired, we used primary osteoblasts isolated from the transgenic mice and showed that BMP signaling is blocked and BMP2-induced mineralized bone matrix formation was inhibited. These studies show the effects of alterations in BMP receptor function targeted to the osteoblast lineage and demonstrate a necessary role of BMP receptor signaling in postnatal bone growth and bone formation in vivo.

Key Words: BMP; receptor; transgenic mice; osteoblast differentiation; bone formation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Yan, Y., Tang, D., Chen, M., Huang, J., Xie, R., Jonason, J. H., Tan, X., Hou, W., Reynolds, D., Hsu, W., Harris, S. E., Puzas, J. E., Awad, H., O'Keefe, R. J., Boyce, B. F., Chen, D. (2009). Axin2 controls bone remodeling through the {beta}-catenin-BMP signaling pathway in adult mice. J. Cell Sci. 122: 3566-3578 [Abstract] [Full Text]  
• David, V., Martin, A., Hedge, A.-M., Rowe, P. S. N. (2009). Matrix Extracellular Phosphoglycoprotein (MEPE) Is a New Bone Renal Hormone and Vascularization Modulator. Endocrinology 150: 4012-4023 [Abstract] [Full Text]  
• Grundberg, E., Brandstrom, H., Lam, K. C. L., Gurd, S., Ge, B., Harmsen, E., Kindmark, A., Ljunggren, O., Mallmin, H., Nilsson, O., Pastinen, T. (2008). Systematic assessment of the human osteoblast transcriptome in resting and induced primary cells. Physiol. Genomics 33: 301-311 [Abstract] [Full Text]  
• Lu, J., Lian, G., Lenkinski, R., De Grand, A., Vaid, R. R., Bryce, T., Stasenko, M., Boskey, A., Walsh, C., Sheen, V. (2007). Filamin B mutations cause chondrocyte defects in skeletal development. Hum Mol Genet 16: 1661-1675 [Abstract] [Full Text]  
• Su, J.-L., Yang, C.-Y., Zhao, M., Kuo, M.-L., Yen, M.-L. (2007). Forkhead Proteins Are Critical for Bone Morphogenetic Protein-2 Regulation and Anti-tumor Activity of Resveratrol. J. Biol. Chem. 282: 19385-19398 [Abstract] [Full Text]  
• Tan, X., Weng, T., Zhang, J., Wang, J., Li, W., Wan, H., Lan, Y., Cheng, X., Hou, N., Liu, H., Ding, J., Lin, F., Yang, R., Gao, X., Chen, D., Yang, X. (2007). Smad4 is required for maintaining normal murine postnatal bone homeostasis. J. Cell Sci. 120: 2162-2170 [Abstract] [Full Text]  
• Wang, Q., Wei, X., Zhu, T., Zhang, M., Shen, R., Xing, L., O'Keefe, R. J., Chen, D. (2007). Bone Morphogenetic Protein 2 Activates Smad6 Gene Transcription through Bone-specific Transcription Factor Runx2. J. Biol. Chem. 282: 10742-10748 [Abstract] [Full Text]  
• Standal, T., Abildgaard, N., Fagerli, U.-M., Stordal, B., Hjertner, O., Borset, M., Sundan, A. (2007). HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood 109: 3024-3030 [Abstract] [Full Text]  
• Zhao, M., Qiao, M., Harris, S. E., Chen, D., Oyajobi, B. O., Mundy, G. R. (2006). The zinc finger transcription factor gli2 mediates bone morphogenetic protein 2 expression in osteoblasts in response to hedgehog signaling.. Mol. Cell. Biol. 26: 6197-6208 [Abstract] [Full Text]  
• Fritz, D. T., Jiang, S., Xu, J., Rogers, M. B. (2006). A Polymorphism in a Conserved Posttranscriptional Regulatory Motif Alters Bone Morphogenetic Protein 2 (BMP2) RNA:Protein Interactions. Mol. Endocrinol. 20: 1574-1586 [Abstract] [Full Text]  
• Kugimiya, F., Kawaguchi, H., Kamekura, S., Chikuda, H., Ohba, S., Yano, F., Ogata, N., Katagiri, T., Harada, Y., Azuma, Y., Nakamura, K., Chung, U.-i. (2005). Involvement of Endogenous Bone Morphogenetic Protein (BMP) 2 and BMP6 in Bone Formation. J. Biol. Chem. 280: 35704-35712 [Abstract] [Full Text]  
• Demirhan, O, Turkmen, S, Schwabe, G C, Soyupak, S, Akgul, E, Tastemir, D, Karahan, D, Mundlos, S, Lehmann, K (2005). A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies. J. Med. Genet. 42: 314-317 [Abstract] [Full Text]  
• Ye, L., Mishina, Y., Chen, D., Huang, H., Dallas, S. L., Dallas, M. R., Sivakumar, P., Kunieda, T., Tsutsui, T. W., Boskey, A., Bonewald, L. F., Feng, J. Q. (2005). Dmp1-deficient Mice Display Severe Defects in Cartilage Formation Responsible for a Chondrodysplasia-like Phenotype. J. Biol. Chem. 280: 6197-6203 [Abstract] [Full Text]  
• Gazzerro, E., Pereira, R. C., Jorgetti, V., Olson, S., Economides, A. N., Canalis, E. (2005). Skeletal Overexpression of Gremlin Impairs Bone Formation and Causes Osteopenia. Endocrinology 146: 655-665 [Abstract] [Full Text]  
• Mishina, Y., Starbuck, M. W., Gentile, M. A., Fukuda, T., Kasparcova, V., Seedor, J. G., Hanks, M. C., Amling, M., Pinero, G. J., Harada, S.-i., Behringer, R. R. (2004). Bone Morphogenetic Protein Type IA Receptor Signaling Regulates Postnatal Osteoblast Function and Bone Remodeling. J. Biol. Chem. 279: 27560-27566 [Abstract] [Full Text]  
• Pereira, R. C., Delany, A. M., Canalis, E. (2004). CCAAT/Enhancer Binding Protein Homologous Protein (DDIT3) Induces Osteoblastic Cell Differentiation. Endocrinology 145: 1952-1960 [Abstract] [Full Text]  
• Zhao, M., Qiao, M., Harris, S. E., Oyajobi, B. O., Mundy, G. R., Chen, D. (2004). Smurf1 Inhibits Osteoblast Differentiation and Bone Formation in Vitro and in Vivo. J. Biol. Chem. 279: 12854-12859 [Abstract] [Full Text]  
• Liu, Z., Shi, W., Ji, X., Sun, C., Jee, W. S. S., Wu, Y., Mao, Z., Nagy, T. R., Li, Q., Cao, X. (2004). Molecules Mimicking Smad1 Interacting with Hox Stimulate Bone Formation. J. Biol. Chem. 279: 11313-11319 [Abstract] [Full Text]  
• Hay, E., Lemonnier, J., Fromigue, O., Guenou, H., Marie, P. J. (2004). Bone Morphogenetic Protein Receptor IB Signaling Mediates Apoptosis Independently of Differentiation in Osteoblastic Cells. J. Biol. Chem. 279: 1650-1658 [Abstract] [Full Text]  
• Zakin, L., De Robertis, E. M. (2004). Inactivation of mouse Twisted gastrulation reveals its role in promoting Bmp4 activity during forebrain development. Development 131: 413-424 [Abstract] [Full Text]  
• Nosaka, T., Morita, S., Kitamura, H., Nakajima, H., Shibata, F., Morikawa, Y., Kataoka, Y., Ebihara, Y., Kawashima, T., Itoh, T., Ozaki, K., Senba, E., Tsuji, K., Makishima, F., Yoshida, N., Kitamura, T. (2003). Mammalian Twisted Gastrulation Is Essential for Skeleto-Lymphogenesis. Mol. Cell. Biol. 23: 2969-2980 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents