Screening of feature genes related to immune and inflammatory responses in periodontitis.

BACKGROUND: Immune and inflammatory responses are important in the occurrence and development of periodontitis. The aim of this study was to screen for immune-related genes and construct a disease diagnostic model to further investigate the underlying molecular mechanisms of periodontitis. METHODS: GSE16134 and GSE10334 datasets were used in this study. Differentially expressed genes (DEGs) between the periodontitis and control groups were selected. Immune-related genes were identified, and functional analysis and construction of an interaction network were conducted. Immune characteristics were evaluated using gene set variation analysis GSVA. Immunity-related modules were analyzed using weighted gene co-expression network analysis (WGCNA). The LASSO algorithm was applied to optimize the module genes. Correlation between optimized immune-related DEGs and immune cells was analyzed. RESULTS: A total of 324 immune-related DEGs enriched in immune- and inflammation-related functions and pathways were identified. Of which, 23 immune cells were significantly different between the periodontitis and control groups. Nine optimal immune-related genes were selected using the WGCNA and LASSO algorithms to construct a diagnostic model. Except for CXCL1, the other eight genes were significantly positively correlated with regulatory T cells, immature B cells, activated B cells, and myeloid-derived suppressor cells. CONCLUSION: This study identified nine immune-related genes and developed a diagnostic model for periodontitis.

Cleft Palate and Aglossia Result From Perturbations in Wnt and Hedgehog Signaling.

OBJECTIVE: The objective of this study was to explore the molecular basis for cleft secondary palate and arrested tongue development caused by the loss of the intraflagellar transport protein, Kif3a. DESIGN: Kif3a mutant embryos and their littermate controls were analyzed for defects in facial development at multiple stages of embryonic development. Histology was employed to understand the effects of Kif3a deletion on palate and tongue development. Various transgenic reporter strains were used to understand how deletion of Kif3a affected Hedgehog and Wnt signaling. Immunostaining for structural elements of the tongue and for components of the Wnt pathway were performed. BrdU activity analyses were carried out to examine how the loss of Kif3a affected cell proliferation and led to palate and tongue malformations. RESULTS: Kif3a deletion causes cranial neural crest cells to become unresponsive to Hedgehog signals and hyper-responsive to Wnt signals. This aberrant molecular signaling causes abnormally high cell proliferation, but paradoxically outgrowths of the tongue and the palatal processes are reduced. The basis for this enigmatic effect can be traced back to a disruption in epithelial/mesenchymal signaling that governs facial development. CONCLUSION: The primary cilium is a cell surface organelle that integrates Hh and Wnt signaling, and disruptions in the function of the primary cilium cause one of the most common-of the rarest-craniofacial birth defects observed in humans. The shared molecular basis for these dysmorphologies is an abnormally high Wnt signal simultaneous with an abnormally low Hedgehog signal. These pathways are integrated in the primary cilium.

Role of Endothelial Progenitor Cells in Maintaining Stemness and Enhancing Differentiation of Mesenchymal Stem Cells by Indirect Cell-Cell Interaction.

A hot issue in current research regarding stem cells for regenerative medicine is the retainment of the stemness and multipotency of stem cell. Endothelial progenitor cells (EPCs) are characterized by an angiogenic switch that induces angiogenesis and further ameliorates the local microenvironment in ischemic organs. This study investigated whether EPCs could modulate the multipotent and differential abilities of mesenchymal stem cells (MSCs) in vitro and in vivo. We established an EPC/MSC indirect Transwell coculture system and then examined the effects of EPCs on the regulation of MSC biological properties in vitro and bone formation in vivo. The in vitro studies showed that cocultured MSCs (coMSCs) display no overt changes in cell morphology but an enhanced MSC phenotype compared with monocultured MSCs (monoMSCs). Our studies regarding the cellular, molecular, and protein characteristics of coMSCs and monoMSCs demonstrated that EPCs greatly promote the proliferation and differentiation potentials of coMSCs under indirect coculture condition. The expression of the pluripotency factors OCT4, SOX2, Nanog, and Klf4 was also upregulated in coMSCs. Furthermore, coMSCs combined with fibrin glue showed improved bone regeneration when used to repair rat alveolar bone defects compared with monoMSC grafts in vivo. This study is the first to demonstrate that EPCs have dynamic roles in maintaining MSC stemness and regulating MSC differentiation potential.

Estrogen-related receptor α is involved in the osteogenic differentiation of mesenchymal stem cells isolated from human periodontal ligaments.

Recently, it has been reported that the orphan nuclear receptor estrogen-related receptor α (ERRα) is involved in the osteogenic differentiation of mesenchymal stem cells (MSCs). Moreover, ERRα has been identified as a novel therapeutic target for treating osteoporosis and other bone diseases. Human periodontal ligament tissue-derived mesenchymal stem cells (hPDLSCs) have recently been used in stem cell-mediated therapies because of their multipotency, particularly toward osteogenic differentiation. However, it is still unclear whether ERRα can regulate the osteogenic differentiation of hPDLSCs. In the present study, we investigated the role of ERRα in the osteogenic differentiation of hPDLSCs in vitro. We isolated hPDLSCs and confirmed their capacity for multipotent differentiation. Furthermore, we examined ERRα expression in hPDLSCs by RT-PCR and immunocytochemistry. We found that the expression of ERRα mRNA was significantly increased during the late stage of osteogenic differentiation of hPDLSCs. Moreover, transfection of recombinant lentiviral-mediated miRNA targeting ERRα significantly suppressed ALP activity, mineralization capacity, and the mRNA expression of osteogenesis-related genes (ALP, OCN, RUNX2 and OPN) in hPDLSCs. Our results indicate that ERRα may promote the osteogenic differentiation of hPDLSCs in vitro.

Progesterone modulates the proliferation and differentiation of human periodontal ligament cells.

Hormone deficiency has been recognized as a risk factor for periodontal disease in postmenopausal women. However, the anabolic effects of progesterone on human periodontal ligament cells (hPDLCs) are still unclear. Therefore, the objective of this study was to detect the expression of progesterone receptor (PgR) in hPDLCs and investigate the bone-sparing effects of progesterone. We detected PgR expression in hPDLCs by reverse transcriptase-polymerase chain reaction and immunocytochemistry. After progesterone stimulation, the percentage of hPDLCs entering the S + G2M phase of the cell cycle increased significantly, accompanied by an increased cell growth curve. In both basic culture medium and osteogenic medium, progesterone activated alkaline phosphatase-positive cells and alizarin red-positive nodules. Moreover, mineralization-related markers were up-regulated by progesterone in both time-dependent and dose-dependent manners. In contrast, these effects of progesterone were blocked by the PgR antagonist (RU486). Our results demonstrated that the PgR is expressed in hPDLCs at the gene and protein level, and that progesterone can stimulate the proliferation and differentiation of the hPDLCs. These findings suggest that progesterone may play a significant role in osteoblastic function of hPDLCs and may influence the maintenance of alveolar bone mass.