CGRP and Shh Mediate the Dental Pulp Cell Response to Neuron Stimulation

Area of Science:

• Neuroscience
• Dental Biology
• Regenerative Medicine

Background:

• Dental pain and pulpitis are significant public health concerns.
• Calcitonin gene-related peptide (CGRP) and Sonic hedgehog (Shh) are implicated in tooth pain and regeneration, but their role in molar pulpitis is unclear.
• Mouse molars share biological similarities with human molars, making them a relevant model.

Purpose of the Study:

• To investigate the role of CGRP and Shh in mouse molar pulpitis.
• To determine if sensory nerves regulate molar pulp cell behavior through CGRP and Shh.
• To explore the potential of CGRP/Shh signaling in managing dental pain and promoting dentin regeneration.

Main Methods:

• Analysis of CGRP receptor and Gli1 expression in molar pulp cells.
• In vivo study of Hedgehog (Hh) signaling activation and Shh expression in a mouse molar injury model.
• In vitro experiments using primary mouse molar and incisor pulp cells, and a human dental pulp stem cell line.
• Treatment with conditioned media from stimulated sensory neurons and inhibition of Shh or CGRP.

Main Results:

• Molar pulp cells express CGRP receptor and Gli1.
• Hh signaling and Shh expression were upregulated in vivo after molar injury.
• Shh and CGRP were found to regulate the differentiation of pulp cells.
• Sensory neuron stimulation induced Hh signaling and inflammatory gene expression in molar pulp cells, which was blocked by Shh or CGRP inhibition.

Conclusions:

• CGRP and Shh signaling may drive inflammation and regulate pulp cell differentiation in molars after injury.
• Activated sensory nerves secrete CGRP and Shh, influencing odontoblast-like cell differentiation for dentin repair.
• CGRP/Shh signaling represents a potential target for new strategies in dental pain management and dentin regeneration.