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Journal of Dental Research
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Biological

Inhibition of Human Dental Pulp Stem Cell Differentiation by Notch Signaling

C. Zhang1, J. Chang2, W. Sonoyama3, S. Shi3 and C.-Y. Wang2,*

1 Department of Special Dental Service, School and Hospital of Stomatology, Peking University, Beijing, China;
2 Laboratory of Molecular Signaling, Division of Oral Biology and Medicine, UCLA School of Dentistry, 10833 Le Conte Ave., Los Angeles, CA 90095, USA; and
3 Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles, CA, USA

Correspondence: * corresponding author, cwang{at}dentistry.ucla.edu

Notch signaling plays a critical role in development and cell fate specification. Notch receptors and ligands have been found to be expressed in dental epithelium or mesenchyme in the developing tooth, suggesting that Notch signaling may regulate odontogenesis. Post-natal human dental pulp stem cells (DPSCs) isolated from the dental pulp have characteristics of mesenchymal stem cells and can differentiate into odontoblasts. In this study, we examined whether Notch signaling regulated the odontoblastic differentiation of DPSCs. We found that over-expression of the Notch ligand, Jagged-1, activated the Notch signaling pathway in DPSCs. Jagged-1 inhibited the odontoblastic differentiation of DPSCs in vitro. Jagged-1-expressing DPSCs could not form mineralized tissues in vivo. Moreover, over-expression of the constitutively activated Notch1 intracellular domain (Notch-ICD) also inhibited odontoblastic differentiation of DPSCs. Taken together, our results demonstrate that Notch signaling can inhibit the odontoblastic differentiation of DPSCs.

Key Words: Notch • dental pulp stem cells • differentiation • tooth development • odontoblasts

Journal of Dental Research, Vol. 87, No. 3, 250-255 (2008)
DOI: 10.1177/154405910808700312
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