NRP1 Accelerates Odontoblast Differentiation of Dental Pulp Stem Cells Through Classical Wnt/β-Catenin Signaling

Abstract

Neuropilin-1 (NRP1) is one of the members of neuropilin family. It can combine with disparate ligands involved in regulating cell proliferation, apoptosis, and differentiation. The binding of NRP1 to Sema3A stimulates osteoblast differentiation through the classical Wnt/β-catenin pathway. However, the functions of NRP1 in dental pulp stem cells (DPSCs) are not clear. The aim of our study was to investigate how NRP1 controlled odontoblast differentiation in DPSCs and clarified the underlying mechanisms. NRP1 expression was increased in time-dependent manner along with cell odontoblast differentiation. Overexpression of NRP1 upregulated dentin matrix protein-1, dentin sialophosphoprotein, alkaline phosphatase protein level, and mineralization in DPSCs, while knockdown of NRP1 induced the opposite effects. SiNRP1 similar to DKK1 availably blocked classical Wnt/β-catenin signaling and odontoblast differentiation. In summary, NRP1, as a promoter of odontoblast differentiation, regulates DPSCs via the classical Wnt/β-catenin pathway.

miR-140-5p regulates the odontoblastic differentiation of dental pulp stem cells via the Wnt1/β-catenin signaling pathway

“…Meanwhile, more and more researches support that the Wnt/β-catenin signaling pathway regulates stem cell self-renewal, proliferation, and differentiation [24–26] and was involved in dental tissue development [27–29]. Our previous study found β-catenin was involved in the odontoblast differentiation of DPSCs, too [6]. In this study, the total and nuclear β-catenin protein levels were the highest in the inhibitor group and the lowest in the mimic group, which indicated miR-140-5p was involved in β-catenin activation.…”

“…The cell culture process was performed as described in our previous studies [6, 20] and approved by the Ethics Committee of the Affiliated Hospital of Nantong University. Briefly, normal human impacted third molars were collected from patients of 14~22 years of age ( n = 10) after they had given informed consent.…”

“…The odontoblastic differentiation process was performed as described in our previous study [6]. Briefly, DPSCs from the fourth passages were cultured in odontogenic differentiation medium containing a Minimum Essential Medium (Invitrogen, Carlsbad, CA), 15% FBS, 10 mmol/L β-glycerophosphate, 50 mg/mL α-ascorbic acid, 10 nmol/L dexamethasone (Sigma-Aldrich, St. Louis, MO), 0.292 mg/mL glutamine, 100 μg/mL streptomycin, and 100 U/mL penicillin for 14 days.…”

“…The results showed that Wnt1 may be one of the target genes of miR-140-5p (more detail is shown in Additional file 1). Our previous study found β-catenin was also involved in the odontoblast differentiation of DPSCs [6]. The Wnt/β-catenin signaling pathway is widely distributed in invertebrates and vertebrates and is a highly conserved signaling pathway during species evolution [13].…”

Vacuolar protein sorting 4B regulates the proliferation and odontoblastic differentiation of human dental pulp stem cells through the Wnt-β-catenin signalling pathway

“…The Wnt signalling pathway substantially participates in multiple cellular processes, including cell migration, proliferation, and differentiation [14,15]. Canonical Wnt signals are transduced via the intracellular mediator b-catenin.…”