Inhibition of Human Dental Pulp Stem Cell Differentiation by Notch Signaling

Abstract

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.

Immunohistochemical expression of p63, epidermal growth factor receptor (EGFR) and notch-1 in radicular cysts, dentigerous cysts and keratocystic odontogenic tumors

“…Notch-1 triggers differentiation and inhibits growth of human keratinocytes in vitro. In the odontogenic tissues, the activation of the Notch signaling may inhibit the differentiation of pulp stem cells into odontoblasts (21), indicating distinct roles of this pathway depending on the analyzed tissue. Genetic deletion of the Notch system in human keratinocytes is sufficient, along with the activation of the ras gene to cause aggressive squamous cell carcinomas (22).…”

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

“…Activation of Notch signaling by Delta1 ligand can enhance the proliferation and odontogenic ability of DPSCs due to the increasing of the proliferation index (PI), DSPP protein expression level and calcifi ed nodules number in Delta1-DPSCs [ 48 ]. However, another study reports that the activation of Notch signaling by either Jagged1 or N1ICD can depress the differentiation of DPSCs into odontoblasts without interrupting cell proliferation [ 92 ]. In addition, Notch signaling pathway modulates the osteogenic differentiation of dental follicle stem cells (DFSCs) [ 93 ].…”

Coculture of Dental Pulp Stem Cells with Endothelial Cells Enhances Osteo-/Odontogenic and Angiogenic Potential In Vitro

“…The odontogenic differentiation potential, the origin from pulp tissue or precursor tissue, and the ability to readily isolate from freshly extracted teeth are the most striking features that make DPSCs a possible candidate for pulp/dentin regeneration (2,3). Previous studies have shown that DPSCs can produce dentin/pulp-like tissues after implantation into tooth slices/fragments and transplantation subcutaneously in immunocompromised mice (4,5).…”