Hypomineralized Enamel Alters Trigeminal Sensory Afferent Architecture, Transcriptome, and Dental Injury Responses
- 1Harvard School of Dental Medicine; Harvard Medical School; Boston University Henry M. Goldman School of Dental Medicine
Abstract
At barrier tissues such as the skin and gut, sensory neurons interface with environmental stimuli and coordinate with neighboring epithelial and immune cells to detect tissue perturbations. In teeth, however, the sensory dentin-pulp complex is insulated from the oral environment by highly mineralized enamel. Although dentin-pulp responses to severe injury have been studied in models with direct pulp exposure, it remains unclear whether enamel barrier dysfunction alone alters pulpal and neuronal homeostasis. Using a kallikrein-related peptidase 4 knockout (KLK4 KO) mouse model of enamel hypomineralization, we demonstrated that defective enamel induced structural, molecular, and transcriptional responses in the dental pulp and in the trigeminal system innervating teeth, despite the absence of direct pulp exposure to the oral cavity. Hypomineralized molars exhibited increased reactionary dentin formation accompanied by retraction of sensory afferents from the dentin-pulp junction. Consistent with these structural findings, trigeminal ganglia of KLK4 KO mice displayed upregulation of genes associated with cytoskeletal remodeling and stimulus response pathways. Despite increased bacterial burden and biofilm accumulation on the enamel surface, enamel hypomineralization did not induce substantial innate immune responses in the pulp. In addition, following severe dental pulp injury, teeth with hypomineralized enamel exhibited reduced sensory afferent loss and tissue damage. Together, these findings reveal that enamel integrity functions as a critical regulator of dentin-pulp homeostasis and that barrier dysfunction alone can precondition tissue responses to subsequent injury.
Related
- Integrative GWAS and Transcriptome Analysis Reveal Genetic Architecture and Candidate Genes for Drought Tolerance During Soybean Germination
- Isoform-Resolved Temporal Remodeling of Transcriptome Architecture in Monkeypox Virus
- Integrated Transcriptome and MicroRNAome Analysis Reveals Dynamic Responses Underlying ZmWAK-Mediated Resistance to Head Smut in Maize
- Beyond the Transcriptome: Chromatin-Informed Prediction of Cell-State-Dependent Perturbation Responses
- Reanalysis of the tomato transcriptome revealed host responses to Southern tomato virus infection
BibTeX
@misc{karaaslan2026hypomineralized,
title = {{Hypomineralized Enamel Alters Trigeminal Sensory Afferent Architecture, Transcriptome, and Dental Injury Responses}},
author = {H. Karaaslan and R. Bossong and E. Wu and L. Alabdulaaly and M. Son and X. He and I. M. Chiu and J. L. Gibbs and F. B. Bidlack and O. Erdogan},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750650},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750650v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Hypomineralized Enamel Alters Trigeminal Sensory Afferent Architecture, Transcriptome, and Dental Injury Responses
AU - H. Karaaslan
AU - R. Bossong
AU - E. Wu
AU - L. Alabdulaaly
AU - M. Son
AU - X. He
AU - I. M. Chiu
AU - J. L. Gibbs
AU - F. B. Bidlack
AU - O. Erdogan
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750650
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750650v1
AB - At barrier tissues such as the skin and gut, sensory neurons interface with environmental stimuli and coordinate with neighboring epithelial and immune cells to detect tissue perturbations. In teeth, however, the sensory dentin-pulp complex is insulated from the oral environment by highly mineralized enamel. Although dentin-pulp responses to severe injury have been studied in models with direct pulp exposure, it remains unclear whether enamel barrier dysfunction alone alters pulpal and neuronal homeostasis. Using a kallikrein-related peptidase 4 knockout (KLK4 KO) mouse model of enamel hypomineralization, we demonstrated that defective enamel induced structural, molecular, and transcriptional responses in the dental pulp and in the trigeminal system innervating teeth, despite the absence of direct pulp exposure to the oral cavity. Hypomineralized molars exhibited increased reactionary dentin formation accompanied by retraction of sensory afferents from the dentin-pulp junction. Consistent with these structural findings, trigeminal ganglia of KLK4 KO mice displayed upregulation of genes associated with cytoskeletal remodeling and stimulus response pathways. Despite increased bacterial burden and biofilm accumulation on the enamel surface, enamel hypomineralization did not induce substantial innate immune responses in the pulp. In addition, following severe dental pulp injury, teeth with hypomineralized enamel exhibited reduced sensory afferent loss and tissue damage. Together, these findings reveal that enamel integrity functions as a critical regulator of dentin-pulp homeostasis and that barrier dysfunction alone can precondition tissue responses to subsequent injury.
ER -