Odontogenesis is well known for its elaborated harmonization of sequential and reciprocal signaling transduction in a spatiotemporal manner at different stages. Bone Morphogenetic Protein 2 (BMP2) has been suggested to play a central and crucial role throughout the entire stages of odontogenesis. Recombinant BMP2 stimulates the secretion of new dentin matrix, and thereby is currently being tested as a molecule for dental reconstruction, as in vital cap therapy. However, the fundamental role of endogenous BMP2 action in dentinogenesis is still unknown. The BMP2 Conditional Knockout mouse model generated by us overcame the limitation of traditional BMP2-null mice which show embryonic lethal at 10.5dpc. Using Tamoxifen-inducible CreERT-loxP system with different odontoblast-specific promoter driving the Cre, the new system now allows us to study the role of BMP2 action in dentinogenesis in the late embryonic stage and postnatally. We hypothesize that BMP2 is necessary for proper dentin formation and plays a crucial signaling role in the process of dentinogenesis at both early odontoblast and late odontoblast stages. The unknown role of BMP2 action in dentinogenesis is expected to be discovered. The potential mechanisms of BMP2 action will be determined by pathway analysis. Expression profiling of genes in primary odontoblasts from wild type and BMP2 deleted odontoblasts will be defined and compared with bioinformatics approaches. The results obtained from the proposed study will advance our understanding of dentinogenesis at a molecular level with, specifically, the molecular pathways involved with dentinogenesis and regulated by BMP2. This study will greatly expand our fundamental knowledge of dentinogenesis and tooth formation, which will lay a profound foundation for designing new and effective therapies for dental defects, such as optimized tooth repair and regeneration.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DE018865-04
Application #
8055310
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Frieden, Leslie A
Project Start
2007-09-01
Project End
2011-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
4
Fiscal Year
2010
Total Cost
$63,332
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Dentistry
Type
Schools of Dentistry
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Rakian, Audrey; Yang, Wu-Chen; Gluhak-Heinrich, Jelica et al. (2013) Bone morphogenetic protein-2 gene controls tooth root development in coordination with formation of the periodontium. Int J Oral Sci 5:75-84
Yang, W; Harris, M A; Cui, Y et al. (2012) Bmp2 is required for odontoblast differentiation and pulp vasculogenesis. J Dent Res 91:58-64
Gluhak-Heinrich, J; Guo, D; Yang, W et al. (2010) New roles and mechanism of action of BMP4 in postnatal tooth cytodifferentiation. Bone 46:1533-45
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