Project description:Periodontal regeneration study. Periodontitis is a common chronic inflammatory disease which may lead to tooth loss. The ultimate goal of periodontal therapy is complete regeneration of the tissues lost as a result of periodontitis. However, most regenerative clinical procedures are unpredictable, largely because there is a lack of understanding of how the various tissues comprising the periodontium (gingival epithelium, gingival connective tissue, periodontal ligament, aveolar bone and cementum) interact during the regenerative process. The aim of this study was to investigate the molecular mechanisms that are involved in periodontal regeneration. For this purpose, paired sets of gingival, ligament and regenerating cells were isolated from patients that have been treated for periodontitis via a regenerative surgical procedure. A microarray analysis using the Hu133A Affymetrix arrays was used to identify the genes and pathways that were characteristic of the three different tissues. We have identified over 500 transcripts in global comparison and intrapatient comparisons that were differentially expressed between ligament and gingival samples, and approximately 30 transcripts that characterized the regenerating cell population. By using a functional classification based on Gene Ontology we were able to group the transcripts into 12 groups. Proteases/Protease inhibitors were differentially expressed between the ligament and gingiva highlighting high ECM remodelling activity by gingival cells. On the other hand, ligament cells were shown to have increased protein synthesis by increasing their nucleolar and ribosomal gene complement. We were able to identify 57 various DNA binding proteins, among them were some well characterised transcription factors, transcriptional regulators, including DNA polymerases and transcriptional co-activators. Furthermore, we have also identified changes in expression of their targets in the two tissues. This is the first study to characterise the gene expression profile of periodontal regenerating cells and allowed us to gain valuable insights into the cellular and molecular mechanisms that occur during the regenerative process. We have identified signalling pathways which are consistent with clinical observations of the regenerative properties of gingival and periodontal ligament cells. These pathways provide candidate targets that can be manipulated in order to achieve a superior regenerative clinical outcome.

Project description:Periodontal regeneration study. Periodontitis is a common chronic inflammatory disease which may lead to tooth loss. The ultimate goal of periodontal therapy is complete regeneration of the tissues lost as a result of periodontitis. However, most regenerative clinical procedures are unpredictable, largely because there is a lack of understanding of how the various tissues comprising the periodontium (gingival epithelium, gingival connective tissue, periodontal ligament, aveolar bone and cementum) interact during the regenerative process. The aim of this study was to investigate the molecular mechanisms that are involved in periodontal regeneration. For this purpose, paired sets of gingival, ligament and regenerating cells were isolated from patients that have been treated for periodontitis via a regenerative surgical procedure. A microarray analysis using the Hu133A Affymetrix arrays was used to identify the genes and pathways that were characteristic of the three different tissues. We have identified over 500 transcripts in global comparison and intrapatient comparisons that were differentially expressed between ligament and gingival samples, and approximately 30 transcripts that characterized the regenerating cell population. By using a functional classification based on Gene Ontology we were able to group the transcripts into 12 groups. Proteases/Protease inhibitors were differentially expressed between the ligament and gingiva highlighting high ECM remodelling activity by gingival cells. On the other hand, ligament cells were shown to have increased protein synthesis by increasing their nucleolar and ribosomal gene complement. We were able to identify 57 various DNA binding proteins, among them were some well characterised transcription factors, transcriptional regulators, including DNA polymerases and transcriptional co-activators. Furthermore, we have also identified changes in expression of their targets in the two tissues. This is the first study to characterise the gene expression profile of periodontal regenerating cells and allowed us to gain valuable insights into the cellular and molecular mechanisms that occur during the regenerative process. We have identified signalling pathways which are consistent with clinical observations of the regenerative properties of gingival and periodontal ligament cells. These pathways provide candidate targets that can be manipulated in order to achieve a superior regenerative clinical outcome. Keywords: other

Project description:Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation.

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Single-Cell and Spatially Resolved Interactomics of Tooth-Associated Keratinocytes in Periodontitis

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