Sensory nerve‐deficient microenvironment impairs tooth homeostasis by inducing apoptosis of dental pulp stem cells

Abstract

Objectives:The aim of this study is to investigate the role of sensory nerve in tooth homeostasis and its effect on mesenchymal stromal/stem cells (MSCs) in dental pulp. Materials and methods:We established the rat denervated incisor models to identify the morphological and histological changes of tooth. The groups were as follows:IANx (inferior alveolar nerve section), SCGx (superior cervical ganglion removal), IANx + SCGx and Sham group. The biological behaviour of dental pulp stromal/ stem cells (DPSCs) was evaluated. Finally, we applied activin B to DPSCs from sensory nerve-deficient microenvironment to analyse the changes of proliferation and apoptosis. Results: Incisor of IANx and IANx + SCGx groups exhibited obvious disorganized tooth structure, while SCGx group only showed slight decrease of dentin thickness, implying sensory nerve, not sympathetic nerve, contributes to the tooth homeostasis. Moreover, we found sensory nerve injury led to disfunction of DPSCs via activin B/SMAD2/3 signalling in vitro. Supplementing activin B promoted proliferation and reduced apoptosis of DPSCs in sensory nerve-deficient microenvironment. Conclusions: This research first demonstrates that sensory nerve-deficient microenvironment impairs tooth haemostasis by inducing apoptosis of DPSCs via activin B/ SMAD2/3 signalling. Our study provides the evidence for the crucial role of sensory nerve in tooth homeostasis.

Sensory nerves, but not sympathetic nerves, promote reparative dentine formation after dentine injury via CGRP‐mediated angiogenesis: An in vivo study

“…The IANx surgery was modified with reference to previous studies (Hayano et al., 2018; Liu et al., 2020). Under deep anaesthesia, a skin extraoral horizontal incision was made to expose the masseter muscle.…”

“…Type H vessels have been identified as a specialized bone-specific vessel type that promotes bone healing (Zhang et al, 2020). However, there have been few studies on the involvement of type H vessels in reparative dentine formation.…”

“…The most well‐known function of dental nerves is to transmit nociceptive signals to the central nervous system, which ultimately evokes the sensation of pain of odontogenic origin. However, accumulating evidence now indicates that dental nerves and nerve‐derived factors also play important roles in regulating the microcirculatory system, immune responses, and tissue repair during the pathophysiological process (Caviedes‐Bucheli et al., 2008; Liu et al., 2020; Maltos et al., 2004). For example, surgical sensory denervation impairs wound healing and tissue survival after pulp exposure (Byers & Taylor, 1993), and systemic application of capsaicin reduces the microhardness of dentine (Krage et al., 2005).…”

Application of dental pulp stem cells in oral maxillofacial tissue engineering

“…Clinically, the inferior alveolar nerve tube is often injured due to trauma or surgery, significantly impairing patients' quality of life. Thus, the use of DPSCs as seed cells to heal the inferior maxillary nerve/inferior alveolar nerve damage is an area that warrants further investigation [84]. Figure 1 below describes the mechanism of DPSCs protection on neural.…”

Dental nerves: a neglected mediator of pulpitis

“…Moreover, changes in pulpal innervation may be partly responsible for degenerative alterations in rodent teeth. Several studies have reported that denervated incisors exhibit reduced microhardness and turn chalky about 1 week after operation and fracture 1 month after denervation (Krage et al 2005, Zhao et al 2014, Hayano et al 2018, Liu et al 2020.…”