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Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair
by
Zhang, Qi
, Zhang, Xiaoyi
, Zhou, Zihao
, Wang, Chunmeng
, Liu, Xiaochen
, Zhou, Jiani
in
Animals
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcitonin
/ Calcitonin gene-related peptide
/ Calcitonin Gene-Related Peptide - genetics
/ Calcitonin Gene-Related Peptide - metabolism
/ Cell Biology
/ Cell culture
/ Cell Differentiation
/ Cell migration
/ Cell Movement
/ Cells, Cultured
/ coculture
/ Denervation
/ Dental pulp
/ Dental Pulp - cytology
/ Dental Pulp - metabolism
/ Gene expression
/ Humans
/ immunohistochemistry
/ Injuries
/ Injury analysis
/ Life Sciences
/ Male
/ Mice
/ Microenvironments
/ Mineralization
/ nerve tissue
/ Nerves
/ Neurons
/ Neuropeptides
/ Original
/ Original Article
/ Proteins
/ pulp
/ Rats
/ Receptor activity modifying proteins
/ Receptor Activity-Modifying Protein 1 - genetics
/ Receptor Activity-Modifying Protein 1 - metabolism
/ Receptors
/ recombinant proteins
/ Regeneration
/ Sensory evaluation
/ Sensory neurons
/ Sensory properties
/ Sensory Receptor Cells - metabolism
/ sequence analysis
/ Signal Transduction
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - metabolism
/ Structure-function relationships
/ tooth pulp
/ Wound Healing - physiology
2024
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Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair
by
Zhang, Qi
, Zhang, Xiaoyi
, Zhou, Zihao
, Wang, Chunmeng
, Liu, Xiaochen
, Zhou, Jiani
in
Animals
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcitonin
/ Calcitonin gene-related peptide
/ Calcitonin Gene-Related Peptide - genetics
/ Calcitonin Gene-Related Peptide - metabolism
/ Cell Biology
/ Cell culture
/ Cell Differentiation
/ Cell migration
/ Cell Movement
/ Cells, Cultured
/ coculture
/ Denervation
/ Dental pulp
/ Dental Pulp - cytology
/ Dental Pulp - metabolism
/ Gene expression
/ Humans
/ immunohistochemistry
/ Injuries
/ Injury analysis
/ Life Sciences
/ Male
/ Mice
/ Microenvironments
/ Mineralization
/ nerve tissue
/ Nerves
/ Neurons
/ Neuropeptides
/ Original
/ Original Article
/ Proteins
/ pulp
/ Rats
/ Receptor activity modifying proteins
/ Receptor Activity-Modifying Protein 1 - genetics
/ Receptor Activity-Modifying Protein 1 - metabolism
/ Receptors
/ recombinant proteins
/ Regeneration
/ Sensory evaluation
/ Sensory neurons
/ Sensory properties
/ Sensory Receptor Cells - metabolism
/ sequence analysis
/ Signal Transduction
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - metabolism
/ Structure-function relationships
/ tooth pulp
/ Wound Healing - physiology
2024
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Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair
by
Zhang, Qi
, Zhang, Xiaoyi
, Zhou, Zihao
, Wang, Chunmeng
, Liu, Xiaochen
, Zhou, Jiani
in
Animals
/ Biochemistry
/ Biomedical and Life Sciences
/ Biomedicine
/ Calcitonin
/ Calcitonin gene-related peptide
/ Calcitonin Gene-Related Peptide - genetics
/ Calcitonin Gene-Related Peptide - metabolism
/ Cell Biology
/ Cell culture
/ Cell Differentiation
/ Cell migration
/ Cell Movement
/ Cells, Cultured
/ coculture
/ Denervation
/ Dental pulp
/ Dental Pulp - cytology
/ Dental Pulp - metabolism
/ Gene expression
/ Humans
/ immunohistochemistry
/ Injuries
/ Injury analysis
/ Life Sciences
/ Male
/ Mice
/ Microenvironments
/ Mineralization
/ nerve tissue
/ Nerves
/ Neurons
/ Neuropeptides
/ Original
/ Original Article
/ Proteins
/ pulp
/ Rats
/ Receptor activity modifying proteins
/ Receptor Activity-Modifying Protein 1 - genetics
/ Receptor Activity-Modifying Protein 1 - metabolism
/ Receptors
/ recombinant proteins
/ Regeneration
/ Sensory evaluation
/ Sensory neurons
/ Sensory properties
/ Sensory Receptor Cells - metabolism
/ sequence analysis
/ Signal Transduction
/ Stem cells
/ Stem Cells - cytology
/ Stem Cells - metabolism
/ Structure-function relationships
/ tooth pulp
/ Wound Healing - physiology
2024
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Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair
Journal Article
Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair
2024
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Overview
Dental pulp stem cells (DPSCs) are responsible for maintaining pulp structure and function after pulp injury. DPSCs migrate directionally to the injury site before differentiating into odontoblast-like cells, which is a prerequisite and a determinant in pulp repair. Increasing evidence suggests that sensory neuron-stem cell crosstalk is critical for maintaining normal physiological functions, and sensory nerves influence stem cells mainly by neuropeptides. However, the role of sensory nerves on DPSC behaviors after pulp injury is largely unexplored. Here, we find that sensory nerves released significant amounts of calcitonin gene-related peptide (CGRP) near the injury site, acting directly on DPSCs via receptor activity modifying protein 1 (RAMP1) to promote collective migration of DPSCs to the injury site, and ultimately promoting pulp repair. Specifically, sensory denervation leads to poor pulp repair and ectopic mineralization, in parallel with that DPSCs failed to be recruited to the injury site. Furthermore, in vitro evidence shows that sensory nerve-deficient microenvironment suppressed DPSC migration prominently among all related behaviors. Mechanistically, the CGRP-Ramp1 axis between sensory neurons and DPSCs was screened by single-cell RNA-seq analysis and immunohistochemical studies confirmed that the expression of CGRP rather than Ramp1 increases substantially near the damaged site. We further demonstrated that CGRP released by sensory nerves binds the receptor Ramp1 on DPSCs to facilitate cell collective migration by an indirect co-culture system using conditioned medium from trigeminal neurons, CGRP recombinant protein and antagonists BIBN4096. The treatment with exogenous CGRP promoted the recruitment of DPSCs, and ultimately enhanced the quality of pulp repair. Targeting the sensory nerve could therefore provide a new strategy for stem cell-based pulp repair and regeneration.
Publisher
Springer International Publishing,Springer Nature B.V
Subject
/ Biomedical and Life Sciences
/ Calcitonin gene-related peptide
/ Calcitonin Gene-Related Peptide - genetics
/ Calcitonin Gene-Related Peptide - metabolism
/ Humans
/ Injuries
/ Male
/ Mice
/ Nerves
/ Neurons
/ Original
/ Proteins
/ pulp
/ Rats
/ Receptor activity modifying proteins
/ Receptor Activity-Modifying Protein 1 - genetics
/ Receptor Activity-Modifying Protein 1 - metabolism
/ Sensory Receptor Cells - metabolism
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