Effects of toothpaste containing surface pre-reacted glass-ionomer (S-PRG) filler on crystallinity and acid resistance of hydroxyapatite.

PURPOSE: To examine the acid resistance of experimental toothpaste containing different wt% of surface pre-reacted glass-ionomer (S-PRG) filler. METHODS: Hydroxyapatite (HAP) pellets were treated with toothpaste containing 0, 1, 5, 10, 20, or 30 wt% S-PRG filler for 5 minutes. A demineralization and remineralization cycle was repeated for 7 days. The demineralized depths of the pellets were measured using a surface roughness analyzer. The crystallinity of both HAP and dicalcium phosphate dehydrate (DCPD) after the S-PRG treatment was measured by a powder X-ray diffraction (XRD) analysis. Fluoride gel (9,000 ppmF) was used for comparison. RESULTS: The demineralizd depth decreased with increases in the S-PRG filler concentration. The demineralized depth with the 30 wt% S-PRG treatment (4.6 µm ± 2.0) was slightly greater than that with the fluoride gel (3.3 µm ± 0.5), but not significantly different (P< 0.05). However, significant differences were observed in demineralized depths between the fluoride gel and the other wt% of S-PRG tested (P< 0.05). In the XRD analysis, no crystallinity changes were noted in HAP or DCPD after the S-PRG or fluoride gel treatments. The formation of calcium fluoride was not detected in any treatment group. CLINICAL SIGNIFICANCE: The results demonstrated the effectiveness of the toothpaste containing 30 wt% S-PRG filler for inhibiting the demineralization of HAP pellets. However, the toothpaste containing S-PRG filler prevented demineralization less effectively than the fluoride gel.

Fluoride activity of antibacterial ammonium hexafluorosilicate solution for the prevention of dentin caries.

PURPOSE: To evaluate the acid resistance of various antibacterial ammonium hexafluorosilicate (SiF) solutions. METHODS: Antibacterial SiF solutions were prepared with the addition of chlorhexidine (CHX), cetylpyridinium chloride (CPC), isopropyl methylphenol (IPMP), or epigallocatechin gallate (EGCG). Hydroxyapatite pellets were treated with SiF solution with or without antibacterial agents for 3 minutes. The demineralized depth of hydroxyapatite pellets after SiF treatment was measured using a surface roughness analyzer. RESULTS: SiF+CPC solution showed equivalent acid resistance to SiF and AgF treatment. In contrast, the original acid resistance activity of SiF solution was diminished by the addition of other antibacterial agents (CHX, IPMP and EGCG). SiF with the addition of CPC was the most effective for reducing the demineralized depth, showing the same levels as those of SiF and AgF. CLINICAL SIGNIFICANCE: The addition of CPC to the SiF solution did not reduce its fluoride activity, indicating that it may be useful for the prevention of dental caries. SiF with added antibacterial agents may have the potential to prevent dental caries.

Antifungal and Mechanical Properties of Tissue Conditioner Containing Plant-Derived Component: An In Vitro Study.

PURPOSE: To evaluate the antifungal activity and mechanical properties of a novel antifungal tissue conditioner containing Juncus powder. MATERIALS AND METHODS: Juncus powder was mixed with GC tissue conditioner at concentrations of 2.5%, 5.0%, and 10.0% by mass. The cylindrical specimens of Juncus-mixed tissue conditioner (dimensions: 10 mm in diameter and 2 and 6 mm in height for antimicrobial and mechanical tests, respectively) were prepared. The specimens placed on the bottom of the 24-well tissue culture plate were cultured with Candida albicans CAD1 for 2 and 4 days. The proliferation of the C. albicans in the wells was determined by measuring the optical density of fungal culture, and the surface of the specimens were also observed by scanning electron microscopy (SEM). To assess the mechanical properties of the specimens, the fluidity and hardness of Juncus-mixed tissue conditioner were measured using the methods certified according to ISO 10139-1. RESULTS: Juncus-mixed tissue conditioner significantly exhibited growth inhibitory effect in a Juncus concentration-dependent manner after both 2- and 4- day cultures. SEM observation showed that the amount of C. albicans on Juncus-mixed specimens drastically decreased, and biofilm formation was markedly inhibited. Moreover, both mechanical properties were found to be within the ranges regulated and specified by ISO. CONCLUSION: These findings demonstrated that the tissue conditioner including Juncus powder has a significant growth inhibitory effect against C. albicans, and it is suggested that the application of Juncus-mixed tissue conditioner may prevent denture stomatitis and oral candidiasis in denture wearers.

IL-29 Enhances CXCL10 Production in TNF-α-stimulated Human Oral Epithelial Cells.

Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay. We used a Western blot analysis to detect IL-29 receptor expression and the phosphorylation levels of signal transduction molecules, including p38 mitogen-activated protein kinases (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor (NF)- κB p65, in the TR146 cells. The TR146 cells expressed the IL-29 receptor. IL-29 induced CXCL10 production in the TR146 cells. IL-29 significantly enhanced CXCL10 production in tumor necrosis factor (TNF)-α-stimulated TR146 cells. The p38 MAPK, STAT3, and NF-κB pathways were found to be related to the IL-29-induced enhancement of CXCL10 production in TNF-α-stimulated TR146 cells. IL-29 promotes T helper 1-cell accumulation in periodontal lesions by inducing CXCL10 production in oral epithelial cells.

Genipin inhibits IL-1ß-induced CCL20 and IL-6 production from human periodontal ligament cells.

BACKGROUND/AIMS: Genipin, the aglycon of geniposide found in gardenia fruit has long been considered for treatment of various diseases in traditional oriental medicine. Genipin has been used as a blue colorant in food industry. Genipin has recently been reported to have some pharmacological functions, such as antimicrobial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether genipin could modify CCL20 and IL-6, which are related to bone resorption in periodontal disease, expression in human periodontal ligament cells (HPDLCs). METHODS: CCL20 and IL-6 productions from HPDLCs were determined by ELISA. Western blot analysis was used for the detection of signal transduction molecules expressions in HPDLCs. RESULTS: Genipin prevented IL-1ß-mediated CCL20 and IL-6 production in HPDLCs. Moreover, genipin could suppress nuclear factor kappa B (NF-κB) p65, extracellular signalregulated kinase (ERK) and MAPK/ERK kinase (MEK) phosphorylations in IL-1ß-stimulated HPDLCs. NF-κB inhibitor and ERK inhibitor significantly inhibited IL-6 and CCL20 productions from IL-1ß-stimulated HPDLCs. CONCLUSIONS: These data provide a novel mechanism through which genipin could be used to provide direct benefits in periodontal disease to inhibit IL-6 and CCL20 productions in periodontal lesions.

(-)-Epigallocatechin-3-gallate inhibits CC chemokine ligand 11 production in human gingival fibroblasts.

BACKGROUND: CC chemokine ligand 11 (CCL11) is related to Th2 cells migration via CC chemokine receptor 3 (CCR3). Th2 cells are involved in the etiology of periodontal disease. However, how the infiltration of Th2 cells is controlled in periodontally diseased tissues is unknown. (-)-Epigallocatechin gallate (EGCG), the major catechin in green tea, has multiple beneficial effects, but the effects of EGCG on CCL11 production are uncertain. In this study, we investigated whether cytokines could induce CCL11 production in human gingival fibroblasts (HGFs). Moreover, we examined the effects of EGCG on CCL11 production in HGFs. METHODS AND RESULTS: ELISA analysis disclosed that interleukin (IL)-4 synergistically enhanced CCL11 production in IL-1ß or tumor necrosis factor (TNF)-α-stimulated HGFs. EGCG prevented IL-1ß/ IL-4 or TNF-α/IL-4-mediated CCL11 production in a concentration dependent manner. CCL11 production in HGFs was positively regulated by p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-Jun N terminal kinase (JNK). Western blot analysis revealed that EGCG treatment prevented IL-1ß/IL-4 or TNF-α/IL-4-induced ERK and JNK activation in HGFs. CONCLUSIONS: These data provide that CCL11 production in HGFs could be associated with Th2 cells infiltration in periodontal lesions. Moreover, EGCG is useful for periodontitis treatment to inhibit CCL11 production.

TLR3 agonist enhances CC chemokine ligand 20 production in IL-1ß-stimulated human gingival fibroblasts.

Viruses are related to the etiology of periodontitis. However, the role of viruses on Th17 cells infiltration in periodontitis lesions is unknown. Therefore, we examined the effects of TLR3 ligand on CCL20, which is related to Th17 cells migration, production in human gingival fibroblasts (HGFs). Polyinosinic-polycytidylic acid (Poly I:C), which is a TLR3 agonist, stimulation could moderately induce CCL20 production in HGFs. Poly I:C synergistically enhanced CCL20 expression from IL-1ß-stimulated HGFs. Inhibitors of p38 MAPK, extracellular signal-regulated kinase (ERK), c-Jun N terminal kinase (JNK), and NF-κB significantly inhibited CCL20 production in Poly I:C/IL-1ß-stimulated HGFs. Western blot analysis disclosed phosphorylation of p38 MAPK, JNK, and IκB-α were enhanced in Poly I:C/IL-1ß-treated HGFs. These data suggested that virus infection is related to Th17 cells migration in periodontitis lesion to induce CCL20 production in HGFs via TLR3. Therefore, our results indicated that virus might be important pathogen in periodontal disease.

Changes in the crystallinity of hydroxyapatite powder and structure of enamel treated with several concentrations of ammonium hexafluorosilicate.

PURPOSE: To evaluate the effects of changing concentrations of ammonium hexafluorosilicate [SiF: (NH4)2SiF6] solution on the crystallinity of hydroxyapatite powder (HAP) and structure of human enamel in order to overcome the tooth discoloration caused by diamine silver fluoride [AgF: (NH3)2AgF] application. METHODS: HAP was treated with several concentrations of SiF solution (from 10 to 19,400 ppm) for 5 minutes. The crystallinity of the HAP before and after SiF treatment was then measured by powder X-ray diffraction (XRD) analysis. The angular width (beta) of the 002 diffraction peak was measured at 1/2 the height of the maximum intensity. Also, enamel specimens were prepared from a human extracted tooth. Several concentrations of SiF solution were applied to polished or phosphoric acid etched enamel specimens. The enamel surface was then observed using scanning electron microscopy (SEM). RESULTS: XRD peaks became sharper after SiF treatment indicating that the crystallinity of apatite powder was increased. The 1/beta value was increased from 2.8 +/- 0.1 to 4.3 +/- 0.1 after treatment with 1,000 ppm SiF solution. The amount of CaF2 formed in HAP was gradually increased with increasing concentrations of SiF solution. TheXRD pattern was consistent with CaF2 in case of over 9,000 ppm SiF solution. SEM photographs demonstrated that exposed enamel rods with acid etching were filled with CaF2-like precipitate after SiF treatment regardless of the concentration of SiF solution.

Antibacterial activity of ammonium hexafluorosilicate solution with antimicrobial agents for the prevention of dentin caries.

PURPOSE: This study evaluated the antibacterial activity of the SiF solution with the addition of antibacterial agents on a Streptococcus mutans biofilm. METHODS: Various antibacterial SiF solutions were prepared by adding chlorhexidine, cetylpyridinium chloride, isopropyl methylphenol, or epigallocatechin gallate. Hydroxyapatite pellets treated with several SiF solutions were immersed in BHI inoculated with S. mutans standardized suspension. The number of S. mutans cells adhered to each pellet was evaluated. RESULTS: SiF with the addition of CPC was the most effective for reducing the adherence of bacteria and inhibiting the formation ofbiofilm, showing the same level as AgF, In contrast, the addition of other antibacterial agents to SiF reduced the original antibacterial activity of SiF solution.

Occlusion of dentin tubules with antibacterial ammonium hexafluorosilicate solution for the prevention of dentin caries.

PURPOSE: To evaluate the degree of penetration of an ammonium hexafluorosilicate [SiF: (NH4)2SiF6] solution containing various antibacterial agents into dentin and the depth of dentin tubule occlusion by the precipitate. METHODS: Various antibacterial SiF solutions were prepared with the addition to chlorhexidine (CHX), cetylpyridinium chloride (CPC), isopropyl methylphenol (IPMP), or epigallocatechin gallate (EGCG), respectively. Two types of dentin disks were prepared from extracted teeth. One was a dentin surface covered with a smear layer, and the other treated with EDTA for 2 minutes to remove the smear layer and open dentin tubules. Then, the disks were treated with SiF solution with or without antibacterial agents for 3 minutes. The dentin surface and a longitudinally divided surface were observed with scanning electron microscopy (SEM) immediately after SiF treatment and after immersion in synthetic saliva for 7 days. RESULTS: SEM photographs demonstrated that dentin tubules after treatment with SiF were occluded homogeneously and similar to those on conventional SiF treatment regardless of the addition of an antibacterial agent. However, the depth of occlusion became significantly shallower when SiF was applied to dentin specimens covered with a smear layer.

Duration of dentin tubule occlusion by the calcium phosphate precipitation method: An in vivo study in beagle dogs.

The aim of the present study was to assess the duration of dentin tubule occlusion by the calcium phosphate precipitation (CPP) method in the vital teeth of beagle dogs. Vital teeth were treated using the CPP method, potassium oxalate, or a bonding agent (Liner bond II) after cavity preparation and acid etching. The dentin tubules of all groups, except for the bonding agent, opened more widely with time in the absence of plaque control. Dentin tubules treated with the CPP method were open and no precipitate remained in the absence of plaque control. Differences were observed in dentin tubule occlusion when plaque control was achieved by daily tooth brushing. The majority of dentin tubules were occluded with an apatitic precipitate seven days after the CPP method with plaque control. The present results demonstrated that the CPP method is useful with proper plaque control.

Oncostatin M synergistically induces CXCL10 and ICAM-1 expression in IL-1beta-stimulated-human gingival fibroblasts.

Periodontitis is a chronic bacterial infection of tooth-supporting structures. T-helper type 1 (Th1) cells are related to the exacerbation of periodontal disease. Human gingival fibroblasts (HGFs), the major cell type in periodontal connective tissues, are involved in immunological response in periodontal tissues. However, it is uncertain whether HGFs are related to Th1 response. Chemokine (C-X-C motif) ligand 10 (CXCL10) is a cytokine, that is related to Th1 cells migration. Intercellular adhesion molecule (ICAM)-1 is involved in Th1 cells retention and activation in inflamed tissue. The aim of this study is to examine the effect of oncostatin M (OSM) on CXCL10 and ICAM-1 expression in HGFs. OSM stimulation induced CXCL10 and ICAM-1 expression in HGFs. Moreover, the synergistic effects of CXCL10 release and ICAM-1 expression in HGFs were observed with combined stimulation of interleukin (IL)-1beta and OSM. OSM increased type 1 IL-1 receptor (IL-1R1) expression, and IL-1beta enhanced OSMRbeta expression on HGFs. IL-1beta + OSM stimulation enhanced the phosphorylation of inhibitor of nuclear factor kappaB (IkappaB)-alpha, signal transducer and activator of transcription (STAT)3, c-Jun N terminal kinase (JNK), and protein kinase B (Akt) compared to OSM or IL-1beta stimulation. CXCL10 production from OSM + IL-1beta stimulated HGFs was suppressed by nuclear factor (NF)-kappaB, STAT3, JNK, and phosphoinositide-3-kinase (PI3K) inhibitors. On the other hand, only NF-kappaB and STAT3 inhibitors suppressed ICAM-1 expression enhanced by OSM + IL-1beta treatment. These effects of OSM and IL-1beta may promote Th1 cells infiltration and retention in periodontally diseased tissues and be related to exacerbation of periodontal disease.

Anti-inflammatory effect of catechin on cultured human dental pulp cells affected by bacteria-derived factors.

Catechins (bioactive polyphenols in green tea) are known to exhibit potent anti-inflammatory properties. However, the anti-inflammatory effects of catechins on inflamed dental pulp tissue are not known. In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG), the major components of green tea catechins, on the expression of pro-inflammatory cytokines and adhesion molecules in human dental pulp cells stimulated with bacteria-derived factors such as lipopolysaccharide (LPS) and peptidoglycan (PG). The expression of interleukin (IL)-6 and of IL-8 was examined using the reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assays. The expression of intercellular adhesion molecule-1 (ICAM-1) and of vascular cell adhesion molecule-1 (VCAM-1) on dental pulp cells was analyzed using flow cytometry. The presence of EGCG and ECG significantly reduced, in a concentration-dependent manner, the expression of IL-6 and IL-8 in dental pulp cells exposed to LPS or PG. Increased expression of ICAM-1 and VCAM-1 on the dental pulp cells in response to bacterial components was also decreased by treatment with EGCG and ECG. These findings suggest that green tea catechins may prevent the exacerbation of pulpitis.

Catechins inhibit CCL20 production in IL-17A-stimulated human gingival fibroblasts.

CC chemokine ligand 20 (CCL20) plays a pivotal role in the recruitment of Th17 cells and thus in the development of periodontal disease. Epigallocatechin gallate (EGCG) and epicatechin gallate (ECG), the major catechins in green tea, have multiple beneficial effects, but the effects of catechins on CCL20 production in human gingival fibroblasts (HGFs) are not known. In this study, we investigated the mechanisms by which EGCG and ECG inhibit interleukin (IL)-17A-induced CCL20 production in human gingival fibroblasts. IL-17A increased CCL20 production in HGFs in a concentration-dependent manner. EGCG and ECG prevented IL-17A-mediated CCL20 production in HGFs. Inhibitors of p38 mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) decreased IL-17A-induced CCL20 production. EGCG and ECG prevented IL-17A-induced phosphorylation of p38 MAPK and ERK in HGFs. In addition, EGCG and ECG attenuated IL-17 receptor expression on HGFs. These data provide a novel mechanism through which the green tea flavonoids catechins could be used to provide direct benefits in periodontal disease.

Carnosic Acid Inhibits CXCR3 Ligands Production in IL-27-Stimulated Human Oral Epithelial Cells.

Carnosic acid, which is a bioactive compound isolated from rosemary, has various pharmacological effects. However, the anti-inflammatory effect of carnosic acid on periodontitis is still unknown. The aim of this study was to investigate the effect of carnosic acid on CXC chemokine receptor 3 (CXCR3) ligands, which are involved in Th1 cells migration and accumulation, production in interleukin (IL)-27-stimulated human oral epithelial cells (TR146 cells). Carnosic acid decreased CXC chemokine ligand (CXCL)9, CXCL10, and CXCL11 production in IL-27-stimulated TR146 cells in a dose-dependent fashion. Moreover, we disclosed that carnosic acid could suppress signal transducer and activator of transcription (STAT)1, STAT3, and protein kinase B (Akt) phosphorylation in IL-27-stimulated TR146 cells. Furthermore, STAT1, STAT3, and Akt inhibitors could suppress CXCR3 ligands production in IL-27-treated TR146 cells. In summary, carnosic acid could reduce CXCR3 ligands production in human oral epithelial cell by inhibiting STAT1, STAT3, and Akt activation.

Caffeic Acid Phenethyl Ester (CAPE) Induces VEGF Expression and Production in Rat Odontoblastic Cells.

Caffeic acid phenethyl ester (CAPE), the main component of propolis, has various biological activities including anti-inflammatory effect and wound healing promotion. Odontoblasts located in the outermost layer of dental pulp play crucial roles such as production of growth factors and formation of hard tissue termed reparative dentin in host defense against dental caries. In this study, we investigated the effects of CAPE on the upregulation of vascular endothelial growth factor (VEGF) and calcification activities of odontoblasts, leading to development of novel therapy for dental pulp inflammation caused by dental caries. CAPE significantly induced mRNA expression and production of VEGF in rat clonal odontoblast-like KN-3 cells cultured in normal medium or osteogenic induction medium. CAPE treatment enhanced nuclear factor-kappa B (NF-κB) transcription factor activation, and furthermore, the specific inhibitor of NF-κB significantly reduced VEGF production. The expression of VEGF receptor- (VEGFR-) 2, not VEGFR-1, was up regulated in KN-3 cells treated with CAPE. In addition, VEGF significantly increased mineralization activity in KN-3 cells. These findings suggest that CAPE might be useful as a novel biological material for the dental pulp conservative therapy.

Ammonium hexafluorosilicate elicits calcium phosphate precipitation and shows continuous dentin tubule occlusion.

UNLABELLED: Diamine silver fluoride [AgF: (NH(3))(2)AgF] has been used clinically in Japan, as it reduces dental caries and dentin hypersensitivity. However, AgF stains the teeth black due to silver precipitation. To overcome this drawback, the authors prepared ammonium hexafluorosilicate [SiF: (NH(4))(2)SiF(6)], which does not stain the teeth, and SiF occluded open dentin tubules completely with silica-calcium phosphate precipitate. OBJECTIVES: The aim of this study was to evaluate the duration of dentin tubule occlusion after SiF treatment in a simulated oral environment. METHODS: To simulate dentin tubules subject to dentin hypersensitivity, dentin disks were treated with EDTA for 2 min. The disks were treated with 0.476 mol/L SiF for 3 min, and then the disks were immersed in synthetic saliva, which was regularly replenished to maintain its ionic concentration, for up to 7 days. The occluding ability of the dentin tubules was evaluated using scanning electron microscopy (SEM), and the hydraulic conductance was measured following Pashley's method at regular intervals. RESULTS: SEM photographs demonstrated that dentin tubules were occluded homogeneously and completely with the precipitate at 7 days after treatment with SiF. In addition, newly formed calcium phosphate precipitate was present at the dentin surface. The dentin permeability showed a consistently low value throughout the experimental period. The values immediately after SiF treatment and 7 days after immersion were 11.9+/-3.7% and 7.9+/-2.9%, respectively. SIGNIFICANCE: Ammonium hexafluorosilicate is useful for the treatment of dentin hypersensitivity, since ammonium hexafluorosilicate induced calcium phosphate precipitation from the saliva; therefore, it has a continuous effect on dentin tubules occlusion under a simulated oral environment.

Effects of calcium phosphate precipitation method on acid resistance to apatite powder and bovine tooth.

The aims of this study were to evaluate the effects of CPP method on the crystallinity of apatite powder and on the acid resistance of bovine enamel. Crystallinity degrees of apatite powder before and after CPP treatment were measured by powder X-ray diffraction analysis. Polished bovine enamel specimens treated with CPP method or NaF were immersed in a lactic acid solution for up to five days. The demineralized depth of enamel was measured with a surface roughness analyzer. XRD peaks became sharper after the CPP treatment, indicating an increased crystallinity of the apatite powder. The demineralized depth of bovine enamel treated with CPP method was shallower than that of enamel treated with NaF. Results of this study revealed that the CPP method increased the crystallinity of apatite powder and the acid resistance of enamel. Therefore, the CPP method would be useful not only for treating dentin hypersensitivity, but also for the prevention of dental caries.

Honokiol and Magnolol Inhibit CXCL10 and CXCL11 Production in IL-27-Stimulated Human Oral Epithelial Cells.

Honokiol and magnolol, which are lignans isolated from Magnolia quinquepeta, have some pharmacological effects. However, the anti-inflammatory effects of honokiol and magnolol on periodontal disease are still uncertain. The aim of this study was to examine the effect of honokiol and magnolol on CXC chemokine receptor 3 (CXCR3) ligands, which are related with Th1 cell migration, production in interleukin (IL)-27-stimulated human oral epithelial cells (TR146 cells). Honokiol and magnolol inhibited CXC chemokine ligand (CXCL)10 and CXCL11 production in IL-27-stimulated TR146 cells in a dose-dependent manner. Moreover, we revealed that honokiol and magnolol could suppress signal transducer and activator of transcription (STAT)3 and protein kinase B (Akt) phosphorylation in IL-27-stimulated TR146 cells though STAT1 phosphorylation was not suppressed by honokiol and magnolol treatment. Furthermore, STAT3 and Akt inhibitors could suppress CXCR3 ligand production in TR146 cells. In summary, honokiol and magnolol could reduce CXCR3 ligand production in oral epithelial cell by inhibiting STAT3 and Akt activation.

The roles of odontoblasts in dental pulp innate immunity.

Odontoblasts located in the outermost layer of dental pulp form a natural barrier between mineralized tissues, dentin, and soft tissues, dental pulp, of the vital tooth, and they first recognize caries-related pathogens and sense external irritations. Therefore, odontoblasts possess a specialized innate immune system to fight oral pathogens invading into dentin. Generally, the rapid initial sensing of microbial pathogens, especially pathogen-associated molecular patterns (PAMPs) shared by microorganisms, are mediated by pattern recognition receptors (PRRs), such as Toll-like receptor and the nucleotide-binding oligomerization domain (NOD). The innate immune responses in odontoblasts initiated by sensing oral pathogens provide host protective events, such as inflammatory reactions, to produce a variety of pro-inflammatory mediators, including chemokines and cytokines. These attract various inflammatory cells and cause antibacterial reactions, such as the production of defensins, to kill microorganisms in the proximal region of the odontoblast layer. This review focuses on innate immunity, especially cellular and molecular mechanisms regarding the sensing of PAMPs from oral pathogens by PRRs, in odontoblasts and provides information for future studies for the development of novel therapeutic strategies, including diagnosis and treatment, to prevent exceeding dental pulp inflammation and preserve the dental pulp tissues.