Proteomic profiling of pulpal and periapical diseases: a systematic review

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Pulpal and periapical diseases represent a significant burden in endodontic practice, yet their molecular pathogenesis remains incompletely understood. Proteomic profiling offers unprecedented opportunities to identify disease-specific biomarkers, elucidate molecular mechanisms, and develop precision diagnostic tools. This systematic review aimed to synthesize the current evidence on proteomic profiling of pulpal and periapical diseases, focusing on key protein biomarkers, molecular pathways, and their potential clinical applications. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science from January 2009 to June 2026. Studies investigating proteomic analyses of human-derived specimens from patients with pulpal and periapical diseases were included, and data extraction and quality assessment were performed according to PRISMA guidelines. Eleven studies involving 577 participants met the inclusion criteria and analyzed diverse biological specimens, including dental pulp tissue, dentinal fluid, root canal samples, and periapical tissue biopsies. Mass spectrometry-based approaches, including LC-MS/MS, MALDI-TOF MS, and 2D-DIGE, identified 1,153 human proteins and 720 microbial proteins (cumulative counts across all included studies) across different disease states. Key biomarkers included S100 family proteins (S100-A8 and S100-A9), heat shock protein 27 (HSP27), peroxiredoxins, myeloperoxidase, serpin family member SERPINB1, hornerin, and hemoglobin subunits. Distinct proteomic signatures differentiated disease stages, symptomatic and asymptomatic presentations, and post-treatment disease states, while enriched molecular pathways involved neutrophil degranulation, oxidative stress, inflammation, pyroptosis, and bone remodeling. Overall, proteomic profiling reveals distinct molecular signatures across the spectrum of pulpal and periapical diseases, providing valuable insights into disease mechanisms and identifying promising diagnostic and prognostic biomarkers. Future studies should focus on validation in larger cohorts, standardization of sampling protocols, and translation of these findings into chairside diagnostic applications. Systematic Review Registration: PROSPERO CRD420261452203.

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