Researchers have created a high-resolution, single-cell map of human gum tissue that could clarify the effects of smoking on periodontitis and highlight a potential target for treatment, according to a recent study.
Although smoking is a known risk factor for periodontitis—which can destroy the tissues that support the teeth and cause tooth loss—the mechanisms behind how tobacco accelerates tissue damage at the cellular level has remained unclear.
In the study, researchers used Visium HD single-cell spatial transcriptomics to analyze gene activity in individual cells while preserving their location in the tissue.
They examined gum tissue samples from healthy controls (n = 4), participants with chronic periodontitis (n = 4), and participants with smoking-related periodontitis (n = 4). The researchers then mapped about 250,000 cells and traced interactions among epithelial, connective tissue, blood vessel, and immune cells.
The results showed that smoking weakens the gum’s epithelial barrier. In smokers with periodontitis, the epithelial cells had altered activity in genes linked to skin-like protective layers, stress responses, and inflammation, signaling structural and functional damage to the mucosal barrier. Laboratory experiments exposing cells to nicotine and bacterial toxins mirrored these changes.
Smoking also altered fibroblasts. For instance, compared with fibroblasts in nonsmokers, the cells in smokers showed higher activity in genes related to aging, cell death, movement, and wound repair. Communication between fibroblasts and epithelial cells was disrupted, potentially promoting excessive cell growth and barrier breakdown.
Immune cells in the gums were also affected. Smoking-associated periodontitis samples had more immune cells, particularly plasma cells and macrophages. Macrophages showed a proinflammatory profile, activating pathways linked to infection sensing and tissue damage. Macrophages were often located close to blood vessel cells, suggesting important interactions.
The researchers noted that changes in blood vessel cells among smokers demonstrated signs of inflammation, DNA damage, and cell death. These cells were the main source of CXCL12, a signaling molecule that interacts with macrophages via the CXCR4 receptor. CXCL12 levels were higher in smoking-related periodontitis compared with in nonsmoking cases. Functional tests revealed that blocking CXCL12 reduced macrophages’ inflammatory activity. In a preclinical model of smoking-induced periodontitis, targeting CXCL12 in blood vessel cells lowered gum inflammation and reduced bone loss around teeth.
The research in this study provided a detailed view of how smoking can accelerate periodontal disease. By damaging the epithelial barrier, altering fibroblast behavior, and amplifying inflammatory interactions between blood vessel cells and macrophages, tobacco use may worsen tissue destruction and tooth loss. According to the researchers, CXCL12 may be a promising target for therapies to slow or prevent smoking-related periodontitis.
The authors declared no competing interests.
