Role and Mechanism of Bone Morphogenetic Protein 2 Action During Dentinogenesis

University Of Texas Hlth Science Center, San Antonio TX

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Abstract

[unreadable] DESCRIPTION (provided by applicant): 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. [unreadable] [unreadable] 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. [unreadable] [unreadable] [unreadable]