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Publication : Constitutive stabilization of ß-catenin in the dental mesenchyme leads to excessive dentin and cementum formation.

First Author  Kim TH Year  2011
Journal  Biochem Biophys Res Commun Volume  412
Issue  4 Pages  549-55
PubMed ID  21854758 Mgi Jnum  J:177539
Mgi Id  MGI:5295356 Doi  10.1016/j.bbrc.2011.07.116
Citation  Kim TH, et al. (2011) Constitutive stabilization of ss-catenin in the dental mesenchyme leads to excessive dentin and cementum formation. Biochem Biophys Res Commun 412(4):549-55
abstractText  Wnt/ss-catenin signaling plays an important role in morphogenesis and cellular differentiation during development. Essential roles of Wnt/ss-catenin signaling in tooth morphogenesis have been well known, but the involvement of Wnt/ss-catenin signaling in the dental hard tissue formation remains undefined. To understand roles of Wnt/ss-catenin signaling in dentin and cementum formation, we generated and analyzed the conditional ss-catenin stabilized mice in the dental mesenchyme. The OC-Cre;Catnb(lox(ex3)/+) mice exhibited malformed teeth characterized by aberrantly formed dentin and excessively deposited cementum. Large amount of dentin was rapidly formed with widened predentin and numerous globular calcifications in the crown. Whereas roots of molars were short and covered with the excessively formed cellular cementum. With age, the coronal pulp chamber and periodontal space were narrowed by the excessively formed dentin and cementum, respectively. To compare the changes of gene expression in the mutant mice, Col1a1 expression was increased but that of Dspp was decreased in the odontoblasts. However, both of Col1a1 and Bsp expression was increased in the cementoblasts. The gene expression changes were consistent with the localization of matrix proteins. Biglycan and PC-1 was increased but Phex was decreased in the odontoblasts and dentin matrix, respectively. TNAP was increased but Dmp1 and FGF23 was decreased in the cementoblasts and cementum matrix, respectively. Our results indicate that persistent stabilization of ss-catenin in the dental mesenchyme leads to premature differentiation of odontoblasts and differentiation of cementoblasts, and induces excessive dentin and cementum formation in vivo. These results suggest that temporospatial regulation of Wnt/ss-catenin signaling plays critical roles in the differentiation of odontoblasts and cementoblasts, and that inhibition of Wnt/ss-catenin signaling may be important for the formation of dentin and cementum during tooth development. Local modulation of Wnt/ss-catenin signaling has therapeutic potential to improve the regeneration of dentin and periodontium.
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