Nicotine destructs dental stem cell-based periodontal tissue regeneration

Nicotine is a widely known addictive and toxic substance in cigarette that exacerbates periodontitis. However, its deleterious effects on dental stem cells and subsequent implications in tissue regeneration remain unclear. This study aimed to explore the effects of nicotine on the regenerative capacity of human periodontal ligament stem cells (hPDLSCs) based on transcriptomics and proteomics, and determined possible targeted genes associated with smoking-related periodontitis.

hPDLSCs were treated with different concentrations of nicotine ranging from 10^-3 to 10^-8 M. Transcriptomics and proteomics were performed and confirmed employing Western blot, 5-ethynyl-2'-deoxyuridine (EdU), and alkaline phosphatase (ALP) staining. A ligature-induced periodontitis mouse model was established and administrated with nicotine (16.2 μg/10 μL) via gingival sulcus. The bone resorption was assessed by micro-computed tomography and histological staining. Key genes were identified using multi-omics analysis with verifications in hPDLSCs and human periodontal tissues.

Based on enrichments analysis, nicotine-treated hPDLSCs exhibited decreased proliferation and differentiation abilities. Local administration of nicotine in mouse model significantly aggravated bone resorption and undermined periodontal tissue regeneration by inhibiting the endogenous dental stem cells regenerative ability. HMGCS1, GPNMB, and CHRNA7 were hub-genes according to the network analysis and corelated with proliferation and differentiation capabilities, which were also verified in both cells and tissues.

Our study investigated the destructive effects of nicotine on the regeneration of periodontal tissues from aspects of in vitro and in vivo with the supporting information from both transcriptome and proteome, providing novel targets into the molecular mechanisms of smoking-related periodontitis.