1259 Osterix Plays a Distinct Role in Root Dentinogenesis through ß-catenin

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
H. ZHANG1, Z. CAO2, Y. LU1, T. GAO1, Y. LIU1, R. D'SOUZA1, and J. FENG1, 1Department of Biomedical Sciences, Texas A&M Health Science Center, Baylor College of Dentistry, Dallas, TX, 2School & Hospital of Stomatology, Wuhan University, Wuhan, China
Objectives: Osterix (Osx) is an essential transcriptional factor for bone (stimulation) and cartilage (inhibition) formation, although its role in dentinogenesis is unknown. The goal of this study was to investigate whether Osx controls tooth root dentin formation by accelerating cell differentiation and mineralization via inhibition of the Wnt/beta-catenin signaling pathway.

Methods: 1) Combined approaches of histology, SEM, micro-CT, x-ray, and double fluorochrome labeling methods were used to characterize the dentin mineralization and tooth root defects in Osx conventional knockout (KO) and conditional knockout (CKO) mice crossed with the 2.3 kb Col 1a1 Cre mice; 2) An odontoblast cell line was transfected with Adv-CMV-Osx and analyzed by real-time RT-PCR and alizarin red S staining; 3) Promoter-luciferase assays  were used to determine the effects of Osx on a 5.4-kb DKK1 (a potent Wnt signaling inhibitor) promoter fragment in COS7 and HEK293 cells.

Results: Osx KO, or Osx CKO mice displayed no apparent changes in crown formation at E18.5 and newborn. In contrast, Osx CKO mice developed a profound root phenotype characterized by short roots (>50%) in both incisors and molars; enlarged pulp chambers/root canals, malformed dentinal tubules and decreased dentin mineralization. Furthermore, there were dramatic reductions in levels of Nestin, and DSPP expression, plus a sharp increase of ß-catenin in Osx CKO pulp and odontoblast cells. Transfection of Osx in an odontoblast cell line significantly increased cell differentiation and mineralization. in vitro Promoter studies demonstrated that Osx was able to activate a 5.4 kb DKK1 promoter fragment with a 3-fold increase of luciferase activity.

Conclusions: These findings suggest that Osterix plays distinct roles in root odontoblast differentiation and mineralization through inhibition of Wnt/beta-catenin signaling.

This abstract is based on research that was funded entirely or partially by an outside source: This research was supported by a Stipend to HZ from NIH/NIDCR T32 (P.I. D’Souza) to RDS, and DE018486 to JQF

Keywords: Dentin, Odontoblasts, Osterix, beta-catenin and Root
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