The inflammatory oral diseases are characterized by the persistent migration of polymorphonuclear leukocytes, monocytes, lymphocytes, plasma and mast cells, and osteoblasts and osteoclasts. In the last decade, there has been a great interest in the mediators responsible for the selective recruitment and activation of these cell types at inflammatory sites. Of these mediators, the chemokines have received particular attention in recent years. Chemokine messages are decoded by specific receptors that initiate signal transduction events, leading to a multitude of cellular responses, including chemotaxis and activation of inflammatory and bone cells. However, little is known about their role in the pathogenesis of inflammatory oral diseases. The purpose of this review is to summarize the findings regarding the role of chemokines in periapical and periodontal tissue inflammation, and the integration, into experimental models, of the information about the role of chemokines in human diseases.

Chemokines in Oral Inflammatory Diseases: Apical Periodontitis and Periodontal Disease

There are several studies about the cytotoxic effects of dental materials in contact with the pulp tissue, such as calcium hydroxide (CH), adhesive systems, resin composite and glass ionomer cements. The aim of this review article was to summarize and discuss the cytotoxicity and biocompatibility of materials used for protection of the dentin-pulp complex, some components of resin composites and adhesive systems when placed in direct or indirect contact with the pulp tissue. A large number of dental materials present cytotoxic effects when applied close or directly to the pulp, and the only material that seems to stimulate early pulp repair and dentin hard tissue barrier formation is CH.

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Cytotoxicity and biocompatibility of direct and indirect pulp capping materials

Dental caries remains one of the most prevalent infectious diseases in the world. So far, available treatment methods rely on the replacement of decayed soft and mineralized tissue with inert biomaterials alone. As an approach to develop novel regenerative strategies and engineer dental tissues, two dental stem cell lines were combined with peptide-amphiphile (PA) hydrogel scaffolds. PAs self-assemble into three-dimensional networks of nanofibers, and living cells can be encapsulated. Cell-matrix interactions were tailored by incorporation of the cell adhesion sequence RGD and an enzyme-cleavable site. SHED (stem cells from human exfoliated deciduous teeth) and DPSC (dental pulp stem cells) were cultured in PA hydrogels for 4 weeks using different osteogenic supplements. Both cell lines proliferate and differentiate within the hydrogels. Histologic analysis shows degradation of the gels and extracellular matrix production. However, distinct differences between the two cell lines can be observed. SHED show a spindle-shaped morphology, high proliferation rates, and collagen production, resulting in soft tissue formation. In contrast, DPSC reduce proliferation, but exhibit an osteoblast-like phenotype, express osteoblast marker genes, and deposit mineral. Since the hydrogels are easy to handle and can be introduced into small defects, this novel system might be suitable for engineering both soft and mineralized matrices for dental tissue regeneration.

Self-Assembling Peptide Amphiphile Nanofibers as a Scaffold for Dental Stem Cells

Comparative characterization of stem cells from human exfoliated deciduous teeth and dental pulp stem cells.

Relationships between caries bacteria, host responses, and clinical signs and symptoms of pulpitis.

Proinflammatory Cytokines Induce Cyclooxygenase-2 mRNA and Protein Expression in Human Pulp Cell Cultures

Aim To investigate the effect of black-pigmented Bacteroides on the expression of interleukin (IL)-8 gene in human pulp fibroblasts and osteoblasts.



Methodology  The supernatants of Porphyromonas endodontalis, P. gingivalis and Prevotella intermedia were used to evaluate IL-8 gene expression in human pulp fibroblasts and osteoblasts. The levels of mRNAs were measured by the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis.



Results  Investigations of the time-dependence of IL-8 mRNA expression in black-pigmented Bacteroides-treated pulp fibroblasts and osteoblasts revealed a rapid accumulation of the transcript after 2 h of exposure, and remained elevated throughout the 24-h incubation period. In addition, IL-8 mRNA gene expression was also found in human osteoblasts stimulated with black-pigmented Bacteroides. However, black-pigmented Bacteroides was found to be more effective in the induction of IL-8 mRNA gene expression in osteoblasts than in pulp fibroblasts (P < 0.05).



Conclusions  Black-pigmented Bacteroides are capable of amplifying the local immune response and promoting pulpal/periapical tissue inflammation by stimulating pulp fibroblasts and osteoblasts to express IL-8.

Induction of interleukin-8 gene expression by black-pigmented Bacteroides in human pulp fibroblasts and osteoblasts.

Aim To investigate the effect of pro-inflammatory cytokines and black-pigmented Bacteroides on the expression of IL-6 gene in human pulp fibroblasts.



Methodology  IL-1α, tumour necrosis factor-α (TNF-α) and the supernatants of Porphyromonas endodontalis, P. gingivalis and Prevotella intermedia were used to evaluate IL-6 gene expression in human pulp fibroblasts. The levels of mRNAs were measured by the quantitative reverse-transcriptase polymerase chain reaction analysis.



Results  Investigations of the time dependence of IL-6 mRNA expression in pro-inflammatory cytokines-treated cells revealed a rapid accumulation of the transcript after 2 h of exposure and remained elevated throughout the 24-h incubation period. In addition, black-pigmented Bacteroides also induced IL-6 gene expression in human pulp fibroblasts.



Conclusions  Pro-inflammatory cytokines and black-pigmented Bacteroides may be involved in developing pulpal inflammation through the stimulation of IL-6 production.

Induction of interleukin-6 gene expression by pro-inflammatory cytokines and black-pigmented Bacteroides in human pulp cell cultures

Induction of cyclooxygenase-2 mRNA and protein expression in human pulp cells stimulated with black-pigmented bacteroides.

Objectives Matrix metalloproteinases (MMPs) play an important role in pulp tissue destruction. However, the mechanisms and signal transduction pathways involved in the production of MMPs in human pulp cells are not fully understood. The purpose of this study was to investigate the gelatinolytic activity in human pulp cells stimulated with various pharmacological agents. Study design Human dental pulp cells were cultured using an explant technique obtained from impacted third molars with informed consent of the patients. The effects of p38 inhibitor SB203580, MEK inhibitor U0126, extracellular signal-regulated kinase (ERK) inhibitor PD098059, phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002, cyclooxygenase-2 (COX-2) inhibitor NS-398, nuclear factor kappa B (NF-κB) inhibitor dexamethasone, and tyrosine kinase inhibitor herbimycin A on the production and secretion of MMPs by human pulp cells were determined by gelatin zymography. Results The main gelatinase secreted by human pulp cells migrated at 72 kd and represented MMP-2. Minor gelatinolytic bands were also observed at 92 kd regions that correspond to MMP-9. After a 4-day culture period, NS-398, dexamethasone, and herbimycin A were found to depress MMP-2 production (P NS-398 > herbimycin A. Human pulp cells, however, treated with various pharmacological agents had no effect on the pattern of MMP-9 produced or secreted in either cell extracts or conditioned medium fractions (P > .05). Conclusion These observations suggest that NS-398, dexamethasone, and herbimycin A can regulate MMP-2 produced by human pulp cells. The signal transduction pathways COX-2, NF-κB, and tyrosine kinase may be involved in the production of MMPs.

Chia-Ming Liu

Papers

Proinflammatory Cytokines Induce Cyclooxygenase-2 mRNA and Protein Expression in Human Pulp Cell Cultures

Induction of interleukin-8 gene expression by black-pigmented Bacteroides in human pulp fibroblasts and osteoblasts.

Induction of interleukin-6 gene expression by pro-inflammatory cytokines and black-pigmented Bacteroides in human pulp cell cultures

Induction of cyclooxygenase-2 mRNA and protein expression in human pulp cells stimulated with black-pigmented bacteroides.

Examination of the signal transduction pathways involved in matrix metalloproteinases-2 in human pulp cells