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Updated: Aug 6, 2026
Establishment of a Murine Pulp Exposure Model with a Novel Mouth-Gag for Pulpitis Research
Published on: October 27, 2023
Integrative Multiomics and Single-cell Profiling Identify Cell-type-resolved Inflammatory Drivers in Symptomatic
Yixin Chen1, Jinsun Jeong2, Hiran Perinpanayagam3
1Department of Endodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong Key Laboratory of Oral Tissue Regeneration and Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration and Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University, Jinan, Shandong, China.
Introduction:
Symptomatic irreversible pulpitis (SIP) is a painful dental condition often diagnosed on the basis of subjective pain reports, which are frequently vague and poorly localized, leading to diagnostic uncertainty and potential overtreatment. Our study integrated multiomics data to identify objective molecular signatures related to pulp inflammation and pain modulation.
Methods:
Proteomic profiling of SIP and healthy pulp was conducted via liquid chromatography-tandem mass spectrometry. Their transcriptional expression was examined in Gene Expression Omnibus dataset to determine consistency across omics levels. Then we used single-cell ribonucleic acid (RNA) sequencing data to map candidate expression to specific pulp cell types. We validated key proteins in pulp tissue by Western blotting. Finally, we quantified selected markers in saliva by enzyme-linked immunosorbent assay as a noninvasive, chairside-adjacent readout and evaluated using receiver operating characteristic analysis.
Results:
Proteomics quantified 5057 proteins. Enrichment analyses highlighted activation of leukocyte-mediated immunity responses and pathways related to nociception. Cross-platform integration identified 6 consistently upregulated molecules (matrix metalloproteinase 9, neutrophil cytosolic factor 2, nuclear factor kappa-B subunit 1, calcium/calmodulin-dependent protein kinase 1, tumor necrosis factor receptor-associated factor 1, and Nucleus Accumbens-Associated Protein 1). Single-cell mapping showed cell-type‑specific expression across macrophages, osteoblast-lineage cells, fibroblasts, and dental pulp stem cells. Tissue validation confirmed upregulation of key candidates, and salivary enzyme-linked immunosorbent assay showed significantly high levels of nuclear factor kappa-B subunit 1 and tumor necrosis factor receptor-associated factor 1 in SIP.
Conclusions:
These findings provide a cell-type‑resolved view of pulpitis-associated inflammatory drivers and may provide candidate molecular readouts for future studies of pulpitis-associated inflammatory activity.