Journal
JOURNAL OF DENTAL RESEARCH
Volume 90, Issue 11, Pages 1312-1317Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0022034511421926
Keywords
DKK1; tooth development; odontoblast; mandibular molar; transgenic mice; dentinogenesis
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Funding
- US National Institutes of Health [DE018486]
- China State Key Laboratory of Oral Diseases [SKLODOF 2010-03]
- National Natural Science Foundation of China [31000419]
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Dickkopf-related protein 1 (DKK1) is a potent inhibitor of Wnt/beta-catenin signaling. Dkk1-null mutant embryos display severe defects in head induction. Conversely, targeted expression of Dkk1 in dental epithelial cells leads to the formation of dysfunctional enamel knots and subsequent tooth defects during embryonic development. However, its role in post-natal dentinogenesis is largely unknown. To address this issue, we studied the role of DKK1 in post-natal dentin development using 2.3-kb Colla1-Dkk1 transgenic mice, with the following key findings: (1) The Dkk1 transgene was highly expressed in pulp and odontoblast cells during post-natal developmental stages; (2) the 1(st) molar displayed short roots, an enlarged pulp/root canal region, and a decrease in the dentin formation rate; (3) a small malformed second molar and an absent third molar; (4) an increase of immature odontoblasts, few mature odontoblasts, and sharply reduced dentinal tubules; and (5) a dramatic change in Osx and nestin expression. We propose that DKK1 controls post-natal mandibular molar dentin formation either directly or indirectly via the inhibition of Wnt signaling at the following aspects: (i) post-natal dentin formation, (ii) formation and/or maintenance of the dentin tubular system, (iii) mineralization of the dentin, and (iv) regulation of molecules such as Osx and nestin.
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