The bone morphogenetic proteins (BMPs) are involved in a variety of developmental and differentiation processes in skin and hair, heart, kidney, reproductive tissues, neural tissues and cartilage, bone and tooth development. In this application, the investigators' major goal is to characterize the mechanisms by which transcription of the BMP2 and BMP4 genes are regulated in osteoblasts and other tissues in vivo and to examine the mechanisms by which BMP2 affects osteoblast function. The stated goals are: 1. To extend prior studies on BMP effects on osteoblasts and chondroblasts and in particular to identify homeobox and other mRNA species which are regulated by BMP2 and which may regulate BMP2 and BMP4 expression during differentiation. 2. To characterize transcriptional regulation of the BMP2 and BMP4 genes in vivo, they will use transgenic mice in which BMP2 or BMP4 gene fragments from the 5' flanking region and other regions are linked to bacterial beta-galactosidase (LacZ) and/or luciferase (LUC). BMP2 and 4 gene transcription control will be examined. Using these mice, genetic crosses to candidate mutant mice can be established to evaluate gene networks and interactions with the BMP2 and BMP4 genes. 3. Using specific regions of the BMP4 promoter driving human BMP4 cDNA that directs expression in the normal BMP4 domains of 6.5-8.5 dpc embryos, the investigators will attempt to rescue the BMP4 homozygous null mutant phenotype. New phenotypes may develop that will give insight into the role of BMP4 later in development.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR044728-02
Application #
2769673
Study Section
Special Emphasis Panel (ZRG4-GRM (03))
Project Start
1997-09-24
Project End
2001-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Yang, Wuchen; Guo, Dayong; Harris, Marie A et al. (2013) Bmp2 in osteoblasts of periosteum and trabecular bone links bone formation to vascularization and mesenchymal stem cells. J Cell Sci 126:4085-98
Yang, Wuchen; Harris, Marie A; Heinrich, Jelica Gluhak et al. (2009) Gene expression signatures of a fibroblastoid preosteoblast and cuboidal osteoblast cell model compared to the MLO-Y4 osteocyte cell model. Bone 44:32-45
Yang, Wuchen; Lu, Yongbo; Kalajzic, Ivo et al. (2005) Dentin matrix protein 1 gene cis-regulation: use in osteocytes to characterize local responses to mechanical loading in vitro and in vivo. J Biol Chem 280:20680-90
Kalajzic, I; Braut, A; Guo, D et al. (2004) Dentin matrix protein 1 expression during osteoblastic differentiation, generation of an osteocyte GFP-transgene. Bone 35:74-82
Gluhak-Heinrich, Jelica; Ye, Ling; Bonewald, Lynda F et al. (2003) Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. J Bone Miner Res 18:807-17
Zhao, Ming; Harris, Stephen E; Horn, Diane et al. (2002) Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. J Cell Biol 157:1049-60
Feng, J Q; Zhang, J; Tan, X et al. (2002) Identification of cis-DNA regions controlling Bmp4 expression during tooth morphogenesis in vivo. J Dent Res 81:6-10
Mundy, G R; Chen, D; Zhao, M et al. (2001) Growth regulatory factors and bone. Rev Endocr Metab Disord 2:105-15
Xu, S C; Harris, M A; Rubenstein, J L et al. (2001) Bone morphogenetic protein-2 (BMP-2) signaling to the Col2alpha1 gene in chondroblasts requires the homeobox gene Dlx-2. DNA Cell Biol 20:359-65
Ghosh-Choudhury, N; Choudhury, G G; Harris, M A et al. (2001) Autoregulation of mouse BMP-2 gene transcription is directed by the proximal promoter element. Biochem Biophys Res Commun 286:101-8

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