Promotion of Dental Pulp Cell Migration and Pulp Repair by a Bioceramic Putty Involving FGFR-mediated Signaling Pathways.
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.
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
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J
Zhang
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
L X
LX
Zhu
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
X
X
Cheng
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Y
Y
Lin
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
P
P
Yan
State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China phs301@vip.163.com.
B
B
Peng
D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D017610:Calcium Compounds / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002516:Ceramics / Q000737:chemistry*; D003782:Dental Pulp / Q000166:cytology* / Q000187:drug effects; D003809:Dentin, Secondary / Q000187:drug effects; D003810:Dentinogenesis / Q000187:drug effects; D004338:Drug Combinations; D051417:Focal Adhesion Kinase 1 / Q000187:drug effects; D022001:Focal Adhesions / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008422:Materials Testing; D008565:Membrane Proteins / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry; D010087:Oxides / Q000494:pharmacology; D051419:Paxillin / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects; D057872:Pulp Capping and Pulpectomy Agents / Q000494:pharmacology*; D051381:Rats; D017468:Receptors, Fibroblast Growth Factor / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D017640:Silicates / Q000494:pharmacology*; D022502:Stress Fibers / Q000187:drug effects; D016596:Vinculin / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects
D017607:Aluminum Compounds; D017610:Calcium Compounds; D004338:Drug Combinations; D008565:Membrane Proteins; D010087:Oxides; D051419:Paxillin; D057872:Pulp Capping and Pulpectomy Agents; C496063:Pxn protein, rat; D017468:Receptors, Fibroblast Growth Factor; D017640:Silicates; C488956:Vcl protein, rat; C000600177:iRoot BP Plus; C086631:mineral trioxide aggregate; D016596:Vinculin; D051417:Focal Adhesion Kinase 1; C496052:Ptk2 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; C535149:Mapk1 protein, rat; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; C031293:calcium silicate
JNK mitogen-activated protein kinase; cell movement; dental pulp capping; extracellular signal-regulated MAP kinase; focal adhesion kinase; proto-oncogene proteins c-akt