Related Experiment Video
Updated: Aug 17, 2026
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
NLRP1 as a Novel Pyroptosis Biomarker in Irreversible Pulpitis: A Laboratory Investigation and Animal Model Study
Jilin Wu1, Churen Zhang2, Jiaqi Chen3
1Department of Cariology and Endodontology, Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Laboratory for Digital and Material Technology of Stomatology; Beijing Key Laboratory of Digital Stomatology; Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health; NMPA Key Laboratory for Dental Materials, Beijing, People's Republic of China.
Aim:
Irreversible pulpitis poses a significant clinical burden due to progressive inflammatory pulp damage. While inflammatory mechanisms are central to its pathogenesis, they remain incompletely characterised. This study aims to elucidate the role of Nod-like receptor thermal domain associated protein 1 (NLRP1) in irreversible pulpitis pathogenesis.
Methodology:
Transcriptomic analysis of public dataset GSE77459 identified dysregulated pyroptosis-related genes (PRGs), with machine learning prioritising hub genes for experimental validation. Key targets were experimentally verified through an integrated approach: in vitro models using lipopolysaccharide (LPS)-stimulated human dental pulp cells (hDPCs) analysed by qRT-PCR, ELISA and Western blot and specific pyroptosis assays (PI uptake, Caspase-1 cleavage); in vivo rat pulpitis models; and clinically validation with human irreversible pulpitis tissues analysed via H&E staining, immunohistochemistry (IHC) and immunofluorescence (IF). Functional roles were further assessed via NLRP1 knockdown and overexpression in hDPCs.
Results:
Bioinformatics identified 11 differentially expressed PRGs, with machine learning highlighting six hub genes including unreported NLRP1. Specific pyroptosis assays confirmed that LPS induces membrane pore formation and Caspase-1 activation in hDPCs. Significant post-transcriptional regulation of NLRP1 was demonstrated by pronounced protein upregulation in LPS-stimulated hDPCs despite unaltered mRNA. Functional studies established NLRP1 as a positive regulator, where its knockdown attenuated the LPS-induced inflammatory-pyroptotic response, while its overexpression alone was sufficient to upregulate key mediators. Consistently, elevated NLRP1 expression was observed in rat models and human tissues, where IHC/IF localised prominent expression to inflammatory infiltrates.
Conclusion:
NLRP1 is highlighted as a novel pyroptosis biomarker for irreversible pulpitis, with its dysregulation offering diagnostic value for inflammation. These findings suggest its potential involvement in the inflammatory mechanisms of pulpitis, providing a new molecular target for future therapeutic exploration.
