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The authors aimed to capture the dynamics of gingival tissue proteome during the initiation and progression of experimental (ligature\u2010induced) periodontitis in mice. Pressure cycling technology (PCT), a recently developed platform that uses ultra\u2010high pressure to disrupt tissues, is utilized to achieve efficient and reproducible protein extraction from ultra\u2010small amounts of gingival tissues in combination with liquid chromatography\u2010tandem mass spectrometry (MS). The MS data are processed using Progenesis QI and the regulated proteins are subjected to METACORE, STRING, and WebGestalt for functional enrichment analysis. A total of 1614 proteins with \u22652 peptides are quantified with an estimated protein false discovery rate of 0.06%. Unsupervised clustering analysis shows that the gingival tissue protein abundance is mainly dependent on the periodontitis progression stage. Gene ontology enrichment analysis reveals an overrepresentation in innate immune regulation (e.g., neutrophil\u2010mediated immunity and antimicrobial peptides), signal transduction (e.g., integrin signaling), and homeostasis processes (e.g., platelet activation and aggregation). 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