# Pulpitis as a microbial disease: single-cell insights into host responses and diagnostic biomarkers for vital pulp therapy

**Authors:** Tiansong Xu, Daishan Yang, Liqi Zhang, Murong Li, Xiuhua Li, Chenggang Duan, Yoo Cheung, Wen Zhang, Zhijian Zhang, Lin Yue, Xiaoying Zou, Feng Chen

PMC · DOI: 10.1080/20002297.2026.2622207 · Journal of Oral Microbiology · 2026-02-17

## TL;DR

This paper explores how microbes and host cells interact in pulpitis, identifying potential biomarkers for better diagnosis and treatment of dental pulp inflammation.

## Contribution

The paper integrates single-cell transcriptomic evidence to reveal infection-specific responses of dental pulp stem cells and identifies microbial and host-derived biomarkers for pulpitis.

## Key findings

- Distinct microorganisms in pulpitis induce diverse inflammatory processes in dental pulp.
- Dental pulp stem cells show infection-specific transcriptional responses linked to inflammation severity.
- Microbial and host biomarkers consistently appear across studies and are validated by single-cell analyses.

## Abstract

Pulpitis is a common dental disease driven by complex microbial infections, yet its microbial origins, diversity, and pathogenic mechanisms remain incompletely understood. A major clinical challenge is the absence of objective biological criteria to assess the severity and reversibility of pulpal inflammation, which is essential for decision-making in vital pulp therapy (VPT).

This review aims to synthesize current evidence on the microbial landscape of pulpitis and to explore microbial- and host-derived biomarkers that may enable objective assessment of inflammation severity and support precision VPT.

We comprehensively reviewed microorganisms implicated in pulpitis and their distinct virulence mechanisms underlying inflammatory responses and tissue damage. Particular emphasis was placed on host responses of dental pulp stem cells (DPSCs) to different microbial infections. Biomarker candidates reported across multiple studies were summarized, and single-cell transcriptomic evidence was integrated to validate microbe-specific DPSC responses.

Distinct microorganisms associated with pulpitis exhibit heterogeneous virulence strategies, inducing diverse inflammatory and degenerative processes within the dental pulp. DPSCs display infection-specific transcriptional responses, revealing molecular signatures linked to inflammation severity and tissue repair potential. Emerging biomarkers derived from both microbial factors and host responses show consistency across studies, with single-cell analyses providing high-resolution validation of these microbe-specific patterns.

Microbial- and host-derived biomarkers hold significant translational potential for stratifying pulpitis severity, informing VPT decision-making, and predicting treatment prognosis. Integrating microbial characterization with host response profiling may advance objective diagnosis and personalized management of pulpitis.

The histopathology of pulpitis is fundamentally driven by the interaction between pathogens and host cells, particularly dental pulp stem cells (DPSCs), which respond by releasing a spectrum of enzymes and cytokines.Single-cell transcriptomic analyses further reveal that this interaction induces both homogeneous and heterogeneous responses across distinct DPSC subclusters.Our findings deepen our understanding of pulpitis pathogenesis and pave the way for improved therapeutic strategies for primary periodontal disease with secondary endodontic involvement.

The histopathology of pulpitis is fundamentally driven by the interaction between pathogens and host cells, particularly dental pulp stem cells (DPSCs), which respond by releasing a spectrum of enzymes and cytokines.

Single-cell transcriptomic analyses further reveal that this interaction induces both homogeneous and heterogeneous responses across distinct DPSC subclusters.

Our findings deepen our understanding of pulpitis pathogenesis and pave the way for improved therapeutic strategies for primary periodontal disease with secondary endodontic involvement.

## Linked entities

- **Diseases:** pulpitis (MONDO:0006937)

## Full-text entities

- **Genes:** TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}, SIRT3 (sirtuin 3) [NCBI Gene 23410] {aka SIR2L3}, FOXO3 (forkhead box O3) [NCBI Gene 2309] {aka AF6q21, FKHRL1, FKHRL1P2, FOXO2, FOXO3A}, CXCL12 (C-X-C motif chemokine ligand 12) [NCBI Gene 449622] {aka SDF1}, CD46 (CD46 molecule) [NCBI Gene 4179] {aka AHUS2, MCP, MIC10, TLX, TRA2.10}, TRPM2 (transient receptor potential cation channel subfamily M member 2) [NCBI Gene 7226] {aka EREG1, KNP3, LTRPC2, LTrpC-2, NUDT9H, NUDT9L1}, TRPM3 (transient receptor potential cation channel subfamily M member 3) [NCBI Gene 80036] {aka CTRCT50, GON-2, LTRPC3, MLSN2, NEDFSS}, PRKCZ (protein kinase C zeta) [NCBI Gene 5590] {aka PKC-ZETA, PKC2}, CXCL10 (C-X-C motif chemokine ligand 10) [NCBI Gene 3627] {aka C7, IFI10, INP10, IP-10, SCYB10, crg-2}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9}, MOK (MOK protein kinase) [NCBI Gene 5891] {aka RAGE, RAGE-1, RAGE1, STK30}, CCL11 (C-C motif chemokine ligand 11) [NCBI Gene 6356] {aka SCYA11}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CCL5 (C-C motif chemokine ligand 5) [NCBI Gene 6352] {aka D17S136E, RANTES, SCYA5, SIS-delta, SISd, TCP228}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, GDF11 (growth differentiation factor 11) [NCBI Gene 10220] {aka BMP-11, BMP11, VHO}, MIP (major intrinsic protein of lens fiber) [NCBI Gene 4284] {aka AQP0, CTRCT15, LIM1, MIP26, MP26}, NOD1 (nucleotide binding oligomerization domain containing 1) [NCBI Gene 10392] {aka CARD4, CLR7.1, NLRC1, hNod1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MMP8 (matrix metallopeptidase 8) [NCBI Gene 4317] {aka CLG1, HNC, MMP-8, PMNL-CL}
- **Diseases:** HIV infection (MESH:D015658), necrosis (MESH:D009336), periodontal and systemic diseases (MESH:D010510), luxations (MESH:D014084), sepsis (MESH:D018805), bacterial infection (MESH:D001424), OCD (MESH:D009771), infective endocarditis (MESH:D004696), SIP (MESH:D011671), dental pulp infection (MESH:D003788), sickle cell anaemia (MESH:D000755), infected (MESH:D007239), VPT (MESH:D016609), oedema (MESH:C536897), dental disease (MESH:D009057), chronic periodontitis (MESH:D055113), gingivitis (MESH:D005891), caries (MESH:D003731), necrobiosis (MESH:D017441), occlusal trauma (MESH:D001157), periodontal pocket (MESH:D010514), hypoxia (MESH:D000860), AIDS (MESH:D000163), pulpal disease (MESH:D003784), periapical lesions (MESH:D010483), Microbial infection (MESH:D015163), bleeding (MESH:D006470), calcification (MESH:D002114), cancer (MESH:D009369), root fractures (MESH:D011843), pus (MESH:D013492), periodontal infections (MESH:D010518), abscess (MESH:D000038), inflammation (MESH:D007249), root canal system infections (MESH:D012141), injuries (MESH:D014947), bacteraemia (MESH:C531821), fibrosis (MESH:D005355), tooth loss (MESH:D016388), apical periodontitis (MESH:D010485), crown fractures (MESH:D050723), pulp necrosis (MESH:D003790)
- **Chemicals:** lipid (MESH:D008055), LPS (MESH:D008070), fluvastatin (MESH:D000077340), phenols (MESH:D010636), NaOCl (MESH:D012973), Pg (-), NO (MESH:D009614), sulphur (MESH:D013455), lactate (MESH:D019344), silver nitrate (MESH:D012835), carbon (MESH:D002244), LTA (MESH:C009900), glucans (MESH:D005936), acid (MESH:D000143), oxygen (MESH:D010100)
- **Species:** Bacteroidia (class) [taxon 200643], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Fusobacterium nucleatum (species) [taxon 851], Propionibacterium (genus) [taxon 1743], human gammaherpesvirus 4 (Epstein Barr virus, no rank) [taxon 10376], Rattus norvegicus (brown rat, species) [taxon 10116], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606], Leptotrichia (genus) [taxon 32067], Porphyromonas gingivalis (species) [taxon 837], Fusobacteriia (class) [taxon 203490], Lacticaseibacillus casei (species) [taxon 1582], Human immunodeficiency virus 1 (no rank) [taxon 11676], Lactobacillus acidophilus (species) [taxon 1579], Actinomycetota (actinobacteria, phylum) [taxon 201174], Actinomyces (genus) [taxon 1654], Capnocytophaga (genus) [taxon 1016], Prevotella intermedia (species) [taxon 28131], Veillonella parvula (species) [taxon 29466], Enterococcus faecalis (species) [taxon 1351], Capnocytophaga periodontitidis (species) [taxon 2795027], Neisseria (genus) [taxon 482], Streptococcus gordonii (species) [taxon 1302], Eubacterium (genus) [taxon 1730], Canis lupus familiaris (dog, subspecies) [taxon 9615], Haemophilus (genus) [taxon 724], Lacticaseibacillus rhamnosus (species) [taxon 47715], Parvimonas (genus) [taxon 543311], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Streptococcus mutans (species) [taxon 1309], Aggregatibacter actinomycetemcomitans (species) [taxon 714], Candida albicans (species) [taxon 5476], Actinomyces naeslundii (species) [taxon 1655], Bacteroidaceae (family) [taxon 815], Lactobacillus sp. (species) [taxon 1591], Escherichia coli (E. coli, species) [taxon 562], Treponema denticola (species) [taxon 158]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12915400/full.md

## References

175 references — full list in the complete paper: https://tomesphere.com/paper/PMC12915400/full.md

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Source: https://tomesphere.com/paper/PMC12915400