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

TLDR

Neuropilin‑1 is a neuropilin family receptor that modulates cell proliferation, apoptosis, and differentiation, and its interaction with Sema3A activates osteoblast differentiation through the classical Wnt/β‑catenin pathway. This study aimed to determine how NRP1 regulates odontoblast differentiation of dental pulp stem cells and to elucidate the underlying mechanisms. NRP1 expression increased during odontoblast differentiation; overexpression enhanced dentin‑matrix protein‑1, dentin sialophosphoprotein, alkaline phosphatase, and mineralization, whereas knockdown had the opposite effect, and siNRP1 blocked Wnt/β‑catenin signaling and differentiation, confirming that NRP1 promotes odontoblast differentiation via the classical Wnt/β‑catenin pathway.

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.