Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabl...Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution,offering new opportunities to investigate these mechanisms.In this study,we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals,including those with periodontitis,those with smoking-associated periodontitis,and healthy controls.Our analysis revealed that smoking disrupts the epithelial barrier integrity,induces fibroblast alterations,and dysregulates fibroblast–epithelial cell communication,thereby exacerbating periodontitis.The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact,which further promotes the progression of smoking-induced periodontal disease.Importantly,we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype,alleviated epithelial inflammation,and reduced alveolar bone resorption.These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial–macrophage interaction as a therapeutic strategy.Furthermore,this study establishes an essential information resource for investigating the effects of smoking on periodontitis,providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.展开更多
MicroRNAs （miRNAs） have been clemonstrated to play an important role in regulation of the immunoinflammatory response; however, the function of miRNAs in periodontal inflammation has not been investigated. The objec...MicroRNAs （miRNAs） have been clemonstrated to play an important role in regulation of the immunoinflammatory response; however, the function of miRNAs in periodontal inflammation has not been investigated. The objective of this study was to explore the properties of miRNAs in periodontal inflammation by comparing miRNA profiles of inflamed and healthy gingival tissues. Gingival tissues were obtained from 10 periodontitis patients and 10 healthy subjects. After RNA extraction, miRNA profiles were analyzed by microarray, and expression levels of selected miRNAs were confirmed by real-time quantitative reverse transcription polymerase chain reaction （RT-PCR）. Analyses using two computational methods, Targetscan and MicroRNA.org, were combined to identify common targets of these miRNAs. Finally, the individual miRNA expression levels of three toll-like receptor （TLR）-related miRNAs from inflamed and healthy gingival tissues were evaluated by RT-PCR. Ninety-one miRNAs were found to be upregulated and thirty-four downregulated over two-fold in inflamed gingival tissue compared with those in healthy gingival tissue. Twelve selected inflammatory-related miRNAs, hsa-miR-126＊, hsa-miR-20a, hsa-miR-142-3p, hsa-miR-19a, hsa-let-7f, hsa-miR-203, hsa-miR-17, hsa-miR-223, hsa-miR-146b, hsa-miR-146a, hsa-miR-155, and hsa-miR-205 showed comparable expression levels by microarray and real-time quantitative RT-PCR analyses. In addition, the putative inflammation targets of these miRNAs were predicted, and three that were tested （hsa-miRNA-146a, hsa-miRNA-146b, and hsa-miRNA-155）, showed significant differences between inflamed and healthy gingiva. This remarkable difference in miRNA profiles between periodontal diseased and healthy gingiva implicates a probable close relationship between miRNAs and periodontal inflammation. The data also suggest that the regulation of TLRs in periodontal inflammation may involve miRNA pathways.展开更多
基金supported by grants from the National Natural Science Foundation of China(Grant nos.82201011,82370958 and 81870770).
文摘Smoking is a well-established risk factor for periodontitis,yet the precise mechanisms by which smoking contributes to periodontal disease remain poorly understood.Recent advances in spatial transcriptomics have enabled a deeper exploration of the periodontal tissue microenvironment at single-cell resolution,offering new opportunities to investigate these mechanisms.In this study,we utilized Visium HD single-cell spatial transcriptomics to profile gingival tissues from 12 individuals,including those with periodontitis,those with smoking-associated periodontitis,and healthy controls.Our analysis revealed that smoking disrupts the epithelial barrier integrity,induces fibroblast alterations,and dysregulates fibroblast–epithelial cell communication,thereby exacerbating periodontitis.The spatial analysis showed that endothelial cells and macrophages are in close proximity and interact,which further promotes the progression of smoking-induced periodontal disease.Importantly,we found that targeting the endothelial CXCL12 signalling pathway in smoking-associated periodontitis reduced the proinflammatory macrophage phenotype,alleviated epithelial inflammation,and reduced alveolar bone resorption.These findings provide novel insights into the pathogenesis of smoking-associated periodontitis and highlight the potential of targeting the endothelial–macrophage interaction as a therapeutic strategy.Furthermore,this study establishes an essential information resource for investigating the effects of smoking on periodontitis,providing a foundation for future research and therapeutic development for this prevalent and debilitating disease.
基金supported by the Science and Tech- nology Commission of Shanghai (Project No. 08JC 1414600)the Doctoral Innovation Fund of Shanghai Jiao Tong University School of Medicine (Project No. BXJ201030) the Shanghai Health Bureau Science Fund for Young Scholars (Project No. 2010165)
文摘MicroRNAs （miRNAs） have been clemonstrated to play an important role in regulation of the immunoinflammatory response; however, the function of miRNAs in periodontal inflammation has not been investigated. The objective of this study was to explore the properties of miRNAs in periodontal inflammation by comparing miRNA profiles of inflamed and healthy gingival tissues. Gingival tissues were obtained from 10 periodontitis patients and 10 healthy subjects. After RNA extraction, miRNA profiles were analyzed by microarray, and expression levels of selected miRNAs were confirmed by real-time quantitative reverse transcription polymerase chain reaction （RT-PCR）. Analyses using two computational methods, Targetscan and MicroRNA.org, were combined to identify common targets of these miRNAs. Finally, the individual miRNA expression levels of three toll-like receptor （TLR）-related miRNAs from inflamed and healthy gingival tissues were evaluated by RT-PCR. Ninety-one miRNAs were found to be upregulated and thirty-four downregulated over two-fold in inflamed gingival tissue compared with those in healthy gingival tissue. Twelve selected inflammatory-related miRNAs, hsa-miR-126＊, hsa-miR-20a, hsa-miR-142-3p, hsa-miR-19a, hsa-let-7f, hsa-miR-203, hsa-miR-17, hsa-miR-223, hsa-miR-146b, hsa-miR-146a, hsa-miR-155, and hsa-miR-205 showed comparable expression levels by microarray and real-time quantitative RT-PCR analyses. In addition, the putative inflammation targets of these miRNAs were predicted, and three that were tested （hsa-miRNA-146a, hsa-miRNA-146b, and hsa-miRNA-155）, showed significant differences between inflamed and healthy gingiva. This remarkable difference in miRNA profiles between periodontal diseased and healthy gingiva implicates a probable close relationship between miRNAs and periodontal inflammation. The data also suggest that the regulation of TLRs in periodontal inflammation may involve miRNA pathways.
