ArticleJournal of oral biology and craniofacial research
E-cigarette aerosol exposure drives extracellular matrix gene dysregulation and collagen remodeling in gingival fibroblasts: An
Article in Journal of oral biology and craniofacial research. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: E-cigarettes are promoted as less harmful alternatives to traditional tobacco products; however, their effects on periodontal tissues and orthodontic outcomes remain unexplored. This study aimed to investigate the impact of e-cigarette aerosol extract (ECAE) on human gingival fibroblasts (hGFs), focusing on cell viability, extracellular matrix (ECM) integrity, gene expression, and nicotine-protein interactions. Methods: Primary hGFs were exposed to ECAE (5-100%) prepared using a standardized puffing protocol. Cell viability was assessed at 24 and 72 h using the MTT assay. ECM-related gene expression with COL1A1, MMP1, MMP9, TIMP1 was quantified by qPCR. Collagen matrix organization and cellular morphology were evaluated using Masson's Trichrome staining and phase-contrast microscopy. Molecular docking was performed to assess nicotine interactions with ECM-associated proteins in 2D and 3D structures. Results: ECAE exposure resulted in a concentration- and time-dependent reduction in fibroblast viability, with significant cytotoxicity observed at concentrations ≥25%. qPCR showed downregulation of COL1A1 and TIMP1, and upregulation of MMP1 and MMP9, indicating a matrix-degradative gene profile. Masson's Trichrome staining revealed reduced collagen deposition and fibrotic band-like structures. Microscopy demonstrated morphological alterations, including cell shrinkage and vacuolation. Docking analysis indicated nicotine binding affinity to COL1A1 with -4.45 kcal/mol and TIMP1 with -5.08 kcal/mol, with stronger affinities for MMP1 with -5.42 kcal/mol and MMP9 (-6.55 kcal/mol), suggesting potential functional interference. Conclusion: ECAE exposure disrupts gingival fibroblast viability and ECM homeostasis through altered gene expression and potential nicotine-protein interactions. These findings suggest potential molecular mechanisms by which e-cigarette aerosols may influence periodontal connective tissue integrity and warrant further investigation using
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