Similar Datasets
Project description:It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-? production from macrophages, and designated this factor, dental pulp cell-derived powerful inducer of TNF-? (DPIT). DPIT was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPIT activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPIT-containing supernatants from pulp cells resulted in activation of both nuclear factor-?B and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, ?-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in dental pulp cells led to reduced DPIT activity. Thus, it appeared that the core protein of DPIT was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPIT for TNF-? induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.
| S-EPMC6405945 | biostudies-literature
Project description:It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived tumor necrosis factor-α-inducing factor (DPTIF). DPTIF was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPTIF activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPTIF-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in pulp cells led to reduced DPTIF activity. Thus, it appeared that the core protein of DPTIF was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPTIF for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.
2018-12-30 | GSE124491 | GEO
Project description:It is well known that dental pulp tissue can evoke some of the most severe acute inflammation observed in the human body. We found that dental pulp cells secrete a factor that induces tumor necrosis factor-α production from macrophages, and designated this factor, dental pulp cell-derived tumor necrosis factor-α-inducing factor (DPTIF). DPTIF was induced in dental pulp cells and transported to recipient cells via microvesicles. Treatment of dental pulp cells with a PKR inhibitor markedly suppressed DPTIF activity, and weak interferon signals were constitutively activated inside the cells. In recipient macrophages, stimulation with DPTIF-containing supernatants from pulp cells resulted in activation of both nuclear factor-κB and MAP kinases like JNK and p38. Proteomics analyses revealed that many stress granule-related proteins were present in supernatants from dental pulp cells as well as microvesicle marker proteins like GAPDH, β-actin, HSPA8, HSPB1, HSPE1, and HSPD1. Furthermore, giant molecule AHNAK and PKR were detected in microvesicles derived from dental pulp cells, and gene silencing of AHNAK in pulp cells led to reduced DPTIF activity. Thus, it appeared that the core protein of DPTIF was PKR, and that PKR was maintained in an active state in stress granule aggregates with AHNAK and transported via microvesicles. The activity of DPTIF for TNF-α induction was far superior to that of gram-negative bacterial endotoxin. Therefore, we, report for the first time, that active PKR is transported via microvesicles as stress granule aggregates and induces powerful inflammatory signals in macrophages.
2018-12-30 | GSE124490 | GEO
Project description:Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles
| PRJNA512198 | ENA
Project description:Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles (pDCvsGF)
| PRJNA512199 | ENA
Project description:Dental pulp cell-derived powerful inducer of TNF-alpha comprises PKR containing stress granule rich microvesicles (GFvsDP-1)
| PRJNA512200 | ENA
Project description:Dental pulp cells can differentiate toward an odontoblastic phenotype to produce reparative dentin beneath caries lesions. However, the mechanisms involved in pulp cell differentiation under pro-inflammatory stimuli have not been well-explored. Thus, we hypothesized that the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) could be a mediator involved in dental pulp cell differentiation toward an odontoblastic phenotype. We observed that TNF-alpha-challenged pulp cells exhibited increased mineralization and early and increased expression of dentin phosphoprotein (DPP), dentin sialoprotein (DSP), dentin matrix protein-1, and osteocalcin during a phase of reduced matrix metalloproteinase (MMP) expression. We investigated whether these events were related and found that p38, a mitogen-activated protein kinase, differentially regulated MMP-1 and DSP/DPP expression and mediated mineralization upon TNF-alpha treatment. These findings indicate that TNF-alpha stimulates differentiation of dental pulp cells toward an odontoblastic phenotype via p38, while negatively regulating MMP-1 expression.
| S-EPMC3144054 | biostudies-literature
Project description:Native dental pulp extracellular matrix (DPEM) has proven to be an effective biomaterial for dental pulp regeneration. However, as a significant extracellular matrix glycoprotein, partial laminins were lost during the decellularization process, which were essential for odontoblast differentiation. Thereby, this study investigated the feasibility of LN supplementation to improve the surface of DPEM for odontoblast layer regeneration. The influences of laminin on cell adhesion and odontogenic differentiation were evaluated in vitro. Then, we fabricated laminin-modified DPEM based on the physical coating strategy and observed the location and persistency of laminin coating by immunofluorescent staining. Finally, laminin-modified DPEM combined with treated dentin matrix (TDM) was transplanted in orthotopic jaw bone of beagles (n = 3) to assess the effect of LNs on dental pulp tissue regeneration. The in vitro results showed that laminins could improve the adhesion of dental pulp stem cells (DPSCs) and promoted DPSCs toward odontogenic differentiation. Continuous odontoblastic layer-like structure was observed in laminin-modified DPEM group, expressing the markers for odontoblastogenesis, dentine matrix protein-1 (DMP-1) and dentin sialophosphoprotein (DSPP). Overall, these studies demonstrate that the supplementation of laminins to DPEM contributes to the odontogenic differentiation of cells and to the formation of odontoblast layer in dental pulp regeneration.
| S-EPMC7838611 | biostudies-literature
Project description:Regenerative endodontic procedures using autologous platelet-rich plasma (PRP) can improve the biologic outcome of treatment. However, its mechanism of action on improving pulp regeneration is not fully elucidated. Autophagy was recently shown to be related to tissue repair and osteogenesis. Therefore, the objective of this study was to investigate the effect of PRP in dental pulp regeneration and to elucidate the role of autophagy involved in this process. Human dental pulp cells (hDPCs) were isolated from healthy dental pulp and co-cultured with an increasing concentration of PRP. Cellular migration and proliferation were determined by scratch assay, transwell assay, and cell-counting kit 8 assay. Osteogenic differentiation was clarified by using alkaline phosphatase staining, alizarin red staining, and real-time polymerase chain reaction (RT-PCR) to measure the gene expression levels of alkaline phosphatase, collagen-1, osteocalcin, dentin matrix protein 1, and dentin sialophosphoprotein. Autophagic bodies were observed by transmission electron microscopy and the expression of autophagy marker light chain 3B (LC3B) was determined by immunofluorescence staining. The mRNA and protein expression level of LC3B and Beclin-1 were quantified by qRT-PCR and western blotting. The effect of PRP on cellular migration, proliferation, and osteogenic differentiation was further investigated in the milieu of autophagy activator, rapamycin, and inhibitor, 3-methyladenine. Results showed that PRP promoted cell migration, proliferation, and osteogenic differentiation. Autophagic bodies were strongly activated and the expression level of LC3B and Beclin-1 was significantly promoted by PRP. Autophagy inhibition suppressed PRP-induced hDPCs migration, proliferation, and osteogenic differentiation, whereas autophagy activator substantially augmented PRP-stimulated migration, proliferation, and differentiation. Taken together, these findings suggested that PRP could effectively promote regenerative potentials associated with autophagy.
| S-EPMC8455824 | biostudies-literature
Project description:Transcriptional response of rat dental pulp cells (DPCs) cultured with SAHA at early and late mineralisation time points Transcript profiling of DPC identified several novel genes expression induced and supressed by HDACi at 24 hrs and 14 days under mineralising conditions. SAHA induces several members of the MMP family of endopepsidases (TIMP-1, MMP-9, MMP-13) and other members of the endochondral ossification pathway at 24 h. 8 experiemental parameters were analysed, each carried out in quadruplicate
2015-06-16 | E-GEOD-67175 | biostudies-arrayexpress