IADR Abstract Archives
Delineating Bone Marrow Microenvironment in Apical Periodontitis via Single-Cell Profiling
Objectives: Apical periodontitis (AP) is a common bacterial infectious disease in the periapical region of teeth. Besides the inflammatory tissue destruction, protective healing process occurs simultaneously, in which mesenchymal stem cells (MSCs) play a primary role. However, a precise picture of the cellular and molecular composition within AP is still scarce.
Methods: We generated a unilateral AP mouse model. Single-cell RNA sequencing using 10x Genomics were applied on alveolar bone in healthy and AP states to identify the cell dynamics and gene expression pattern. Immunostaining and quantitative real-time PCR were performed to investigate the expression pattern of MSCs using transgenic mouse models and human alveolar bone samples in patients with AP.
Results: We investigated cellular changes in frequency and expression pattern relevant to AP, as well as the interactions between MSCs and immunocytes. The results highlighted the enhanced self-supporting network and osteogenic potential within MSC cluster under AP. We also defined key AP-associated MSC subclusters and their biomarkers. Under AP conditions, MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher level of osteogenic molecules, which were confirmed by transgenic mouse models and human alveolar bone samples from AP lesions.
Conclusions: In summary, the current study elucidated an in-depth picture of mandibular MSCs and immunocytes in steady and AP states, which promoted the understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. These findings have implications for designing new therapeutic targets and approaches to restore AP and other related inflammatory bone diseases.
Methods: We generated a unilateral AP mouse model. Single-cell RNA sequencing using 10x Genomics were applied on alveolar bone in healthy and AP states to identify the cell dynamics and gene expression pattern. Immunostaining and quantitative real-time PCR were performed to investigate the expression pattern of MSCs using transgenic mouse models and human alveolar bone samples in patients with AP.
Results: We investigated cellular changes in frequency and expression pattern relevant to AP, as well as the interactions between MSCs and immunocytes. The results highlighted the enhanced self-supporting network and osteogenic potential within MSC cluster under AP. We also defined key AP-associated MSC subclusters and their biomarkers. Under AP conditions, MSCs not only differentiated towards osteoblast lineage cells, but also expressed higher level of osteogenic molecules, which were confirmed by transgenic mouse models and human alveolar bone samples from AP lesions.
Conclusions: In summary, the current study elucidated an in-depth picture of mandibular MSCs and immunocytes in steady and AP states, which promoted the understanding of heterogeneity and cellular interactions of alveolar bone cells under pathogenic and inflammatory conditions. These findings have implications for designing new therapeutic targets and approaches to restore AP and other related inflammatory bone diseases.