ABSTRACT: 0558

BMP2 is Necessary for Late Stages in Odontogenesis postnatally

W. YANG¹, D. GUO², J. GLUHAK-HEINRICH³, M.A. HARRIS¹, A. LICHTLER⁴, B.E. KREAM⁴, J.Q. FENG⁵, Y. MISHINA⁶, and S.E. HARRIS⁷, ¹U. of Texas Health Science Center at San Antonio, USA, ²University of Missouri -Kansas City, USA, ³University of Texas - San Antonio / Health Science Ctr, USA, ⁴University of Connecticut, Farmington, USA, ⁵Baylor College of Dentistry, Texas A&M Health Science Center, Dallas, USA, ⁶NIEHS/NIH, Research Triangle Park, NC, USA, ⁷UTHSC at San Antonio, TX, USA

Bone Morphogenetic Protein 2 (BMP2) is expressed at several stages in odontogenesis. The role of BMP2 in odontogenesis is unknown due to the embryonic lethality of the standard BMP2 KO model.

Objectives: To define the function and mechanism of endogenous BMP2 action in dentinogenesis postnatally.

Methods: BMP2 floxed mice were crossed with the 3.6Col1a1-promoter driving Cre-recombinase in collagen type 1 expressing cells. The efficiency of the deletion of BMP2 was confirmed by in situ hybridization. X-rays and histomorphometric analysis were utilized to characterize the mineralization and morphological changes of teeth after BMP2 conditional deletion postnatally. Quantitative in situ hybridization with early and late odontoblast expressed genes and immunocytochemistry analysis on Phospho-Smad1/5/8 signaling were determined at several stages of tooth cytodifferentiation.

Results: Deletion of BMP2 gene at or near birth disrupts postnatal odontogenesis. BMP2 expression in odontoblasts was effectively deleted as shown by decreased expression of BMP2 by over 85%. X-ray observations at 12 days showed the teeth were hypomineralized with a 35% reduction in dentin thickness, and a corresponding increase in the pulp chamber. Standard histomorphometric analysis confirmed the decreased dentin thickness and demonstrated a failure for the dentin to mature. This was confirmed by demonstrating a 90% reduction in osteocalcin and a 75% reduction in DSPP expression, both late markers of odontogenesis. Genes such as DMP1 and BMP4, expressed early in odontogenesis showed elevated expression of 50% to 70%. Phospho-Smad1/5/8 also showed increased expression in the very early pre-polarizing stages. These results suggest that early odontoblast cells are piling up and failing to progress to the more mature stages in the absence of BMP2.

Conclusion: BMP2 is required for proper progression of odontogenesis to late stages of tooth formation in postnatal animals.

Supported by NIDCR Grant DE018865, NIAMS Grant R01-AR054616

Seq #87 - Keynote Address and Genetic Mutations
8:00 AM-9:30 AM, Friday, April 4, 2008
Hilton Anatole Hotel Emerald

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