Abstract
Notch signaling regulates diverse biological processes in dental pulp tissue. The present study investigated the response of human dental pulp cells (hDPs) to the indirect immobilized Notch ligand Jagged1 in vitro. The indirect immobilized Jagged1 effectively activated Notch signaling in hDPs as confirmed by the upregulation of HES1 and HEY1 expression. Differential gene expression profiling using an RNA sequencing technique revealed that the indirect immobilized Jagged1 upregulated genes were mainly involved in extracellular matrix organization, disease, and signal transduction. Downregulated genes predominantly participated in the cell cycle, DNA replication, and DNA repair. Indirect immobilized Jagged1 significantly reduced cell proliferation, colony forming unit ability, and the number of cells in S phase. Jagged1 treated hDPs exhibited significantly higher ALP enzymatic activity, osteogenic marker gene expression, and mineralization compared with control. Pretreatment with a γ-secretase inhibitor attenuated the Jagged1-induced ALP activity and mineral deposition. NOTCH2 shRNA reduced the Jagged1-induced osteogenic marker gene expression, ALP enzymatic activity, and mineral deposition. In conclusion, indirect immobilized Jagged1 suppresses cell cycle progression and induces the odonto/osteogenic differentiation of hDPs via the canonical Notch signaling pathway.
Highlights
Notch signaling is activated via direct cell-cell interaction as both Notch receptors and ligands are transmembrane proteins[1]
Previous reports demonstrated that Notch activation promotes osteogenic differentiation in various cell types, including human periodontal ligament stem cells, stem cells isolated from human exfoliated deciduous teeth (SHEDs), and human bone marrow mesenchymal stem cells[8,9,10,11,12]
The present study investigated the differential gene expression profile of Human dental pulp cells (hDPs) after treatment with indirect immobilized Jagged[1] compared with the the human IgG Fc fragment (hFc) immobilized control cells
Summary
Notch signaling is activated via direct cell-cell interaction as both Notch receptors and ligands are transmembrane proteins[1]. Notch signaling is activated in dental pulp tissue treated with calcium hydroxide, with the expression of Hes[1] observed near the exposure site and along the adjacent dentin walls[3]. This finding implies that the activation of Notch signaling after calcium hydroxide pulp capping might regulate pulp cell differentiation toward odontoblast-like cells and perivascular cells, subsequently promoting dentin bridge formation[3]. Role for Notch in inflammation[2] These data indicate the multi-functional regulation of Notch signaling in dental pulp cells. Overexpressing Notch ligand or NICD inhibited odontogenic differentiation in human dental pulp stem cells[7]. The present study investigated the differential gene expression profile of hDPs after treatment with indirect immobilized Jagged[1] compared with the the hFc immobilized control cells
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