Promotion of Dental Pulp Cell Migration and Pulp Repair by a Bioceramic Putty Involving FGFR-mediated Signaling Pathways

Abstract

Mineral trioxide aggregate is the currently recommended material of choice for clinical pulp repair despite several disadvantages, including handling inconvenience. Little is known about the signaling mechanisms involved in bioceramic-mediated dental pulp repair-particularly, dental pulp cell (DPC) migration. This study evaluated the effects of iRoot BP Plus, a novel ready-to-use nanoparticulate bioceramic putty, on DPC migration in vitro and pulp repair in vivo, focusing on possible involvement of fibroblast growth factor receptor (FGFR)-related signaling, including mitogen-activated protein kinase and Akt pathways. Treatment with iRoot BP Plus extracts enhanced horizontal and vertical migration of DPCs, which was comparable with the effects induced by mineral trioxide aggregate extracts. The DPCs exposed to iRoot BP Plus extracts demonstrated no evident apoptosis. Importantly, treatment with iRoot BP Plus extracts resulted in rapid activation of FGFR, p38 mitogen-activated protein kinase, extracellular signal-regulated kinase (ERK) 1/2, c-Jun-N-terminal kinase (JNK), and Akt signaling in DPCs. Confocal immunofluorescence staining revealed that iRoot BP Plus stimulated focal adhesion formation and stress fiber assembly in DPCs, in addition to upregulating the expression of focal adhesion molecules, including p-focal adhesion kinase, p-paxillin, and vinculin. Moreover, activation of FGFR, ERK, JNK, and Akt were found to mediate the upregulated expression of focal adhesion molecules, stress fiber assembly, and enhanced DPC migration induced by iRoot BP Plus. Consistent with the in vitro results, we observed induction of homogeneous dentin bridge formation and expression of p-focal adhesion kinase, p-FGFR, p-ERK 1/2, p-JNK, and p-Akt near injury sites by iRoot BP Plus in an in vivo pulp repair model. These data demonstrate that iRoot BP Plus can promote DPC migration and pulp repair involving the FGFR-mediated ERK 1/2, JNK, and Akt pathways. These findings provide valuable insights into the signaling mechanisms underlying nanoparticulate bioceramic-mediated pulp repair.

Comparative analysis of the biological effects of the endodontic bioactive cements MTA‐Angelus, MTA Repair HP and NeoMTA Plus on human dental pulp stem cells

“…Cell adhesion and migration require cytoskeletal reorganization and focal adhesion molecule expression, so the optimum state of dental pulp cells is a critical aspect that contributes to cell migration and finally to dental pulp repair (Zhang et al . , Lv et al . ).…”

Signaling Pathways in Dental Stem Cells During Their Maintenance and Differentiation

“…JNK and p38 inhibitors can affect F-actin remodeling induced by HGF and thus, contribute to HGF-induced migration [ 22 ]. The activation of fi broblast growth factor receptor (FGFR), ERK, JNK, and AKT can modulate the upregulation of focal adhesion molecules, stress fi ber assembly, and enhance cell migration induced by iRoot BP Plus [ 23 ]. ERK determines cell movement by the phosphorylation of myosin light chain kinase (MLCK), calpain or focal adhesion kinase (FAK).…”

What do different tests tell about the mechanical and biological properties of bioceramic materials?

“…(E) Cell apoptosis of the DPSC s exposed to the extracts from iR oot BP Plus and MTA measured by flow cytometry after Annexin V‐ PI staining. Reproduced from Zhang et al, 2015 .…”

“…The horizontal (C) and vertical (D) migrated cells were counted and presented as percentages relative to the control group. Reproduced from Zhang et al, 2015 .…”

“…(B) The relative expression ratio of p‐ FAK / FAK , p‐paxillin/paxillin, and vinculin/β‐actin was calculated based on the band intensity of Western blot. Reproduced from Zhang et al, 2015 .…”