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Updated: Jul 13, 2026
Induction of Periodontitis via a Combination of Ligature and Lipopolysaccharide Injection in a Rat Model
Published on: February 17, 2023
Integrated network toxicology, machine learning, molecular docking and experimental validation to elucidate mechanism
Yaoling Han1, Zhengchuan Zhang1, Zijun Wang1
1Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou 510080, China; Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510080, China.
Abstract:
Growing evidence highlights the health risks of micro-plastics (MPs) exposure, with reported accumulations in enclosed anatomical sites such as the heart, placenta, and circulatory system. However, the role of MPs in periodontitis remains unexplored. This study employed bioinformatics, network toxicology, machine learning, molecular docking, and experimental approaches to explore the effects and underlying mechanisms of polyethylene terephthalate microplastics (PET-MPs) induced periodontitis. Multi-database screening, including GEO, ChEMBL, STITCH, GeneCards, OMIM, identified 23 candidate targets linked to PET-MPs exposure. Furthermore, we used STRING, Cytoscape software and machine learning approaches to identified 13 core targets. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and immune cell infiltration analyses revealed that PET-MPs influence immune-related pathways, such as C-type lectin receptor signaling, VEGF receptor signaling, and TNF signaling. Molecular docking revealed high-affinity binding interactions between PET-MPs and core targets, implicating direct interference with cellular processes. Experimental assays using gingival fibroblasts (GFs) exposed to PET-MPs showed dose-dependent cytotoxicity oxidative stress induction, and pro-inflammatory activation. PET-MPs upregulated inflammation-related markers including Caspase 3, KDR, PIM2, PTGS2, MTOR, MAPK14; while downregulating AKT1 and ALPL. These findings establish a mechanistic framework linking PET-MPs exposure to periodontitis progression via redox-inflammatory crosstalk, offering novel insight into the potential pathogenesis of microplastics on periodontitis.
Insights
Polyethylene terephthalate microplastics (PET-MPs) exposure is linked to periodontitis. This study reveals PET-MPs induce cytotoxicity, oxidative stress, and inflammation in gingival cells, contributing to gum disease progression.
Area of Science:
- Environmental Health
- Toxicology
- Oral Biology
Background:
- Microplastics (MPs) pose health risks, accumulating in various organs.
- The impact of MPs on periodontitis is currently unknown.
- Polyethylene terephthalate microplastics (PET-MPs) are common environmental pollutants.
Purpose of the Study:
- To investigate the effects of PET-MPs on periodontitis.
- To elucidate the underlying molecular mechanisms of PET-MPs-induced periodontitis.
- To explore the role of redox-inflammatory pathways in this process.
Main Methods:
- Bioinformatics, network toxicology, machine learning, and molecular docking were employed.
- Candidate and core gene targets associated with PET-MPs exposure were identified.
- Experimental assays on gingival fibroblasts (GFs) assessed cytotoxicity, oxidative stress, and inflammation.
Main Results:
- PET-MPs exposure was linked to 13 core targets and influenced immune-related pathways (e.g., C-type lectin receptor, VEGF, TNF signaling).
- Molecular docking indicated direct interactions between PET-MPs and core targets.
- Experimental data showed PET-MPs induced dose-dependent cytotoxicity, oxidative stress, and pro-inflammatory responses in GFs, altering key marker expressions.
Conclusions:
- PET-MPs exposure can induce periodontitis through redox-inflammatory crosstalk.
- This study provides a mechanistic link between microplastic exposure and the pathogenesis of periodontitis.
- Findings highlight potential risks of PET-MPs to oral health.
