The association of MMP-9 and IL-18 gene promoter polymorphisms with gingivitis in adolescents

Objective

Interleukin 18 (IL-18) is shown to be a proinflammatory cytokine that regulates the expression of matrix metalloproteinase 9 (MMP-9). The aim of this study was to test for differences between Czech adolescents with and without gingivitis in relation to MMP-9 and IL-18 polymorphisms.

Design

A total of 298 Caucasian children, aged 11-13 years, were examined to assess gingival health. DNA for genetic analysis was obtained from buccal epithelial cells, and the MMP-9 −1562C/T and IL-18 −607A/C variants were identified with PCR-RFLP.

Results

Gingivitis was present in 49.3% of the adolescents examined, the rest of the group was considered healthy. The IL-18 −607C and MMP-9 −1562T alleles were found in 58.9% and 8.3% of the healthy subjects, and in 62.2% and 15.0% of the patients with gingivitis, respectively. Although differences in allele frequencies were not significant for IL-18 variant, they were significant for MMP-9 polymorphism (p = 0.01, p_corr < 0.05). Furthermore, a highly significant association of the composite genotype (formed by the variants of the both genes) with gingivitis was found (p = 0.004, p_corr < 0.05).

Conclusions

The −1562 T allele of MMP-9 gene could have a role in gingivitis in adolescents. In addition, interaction of the MMP-9 and IL-18 genes could be considered a risk factor for the development of gingivitis in children.     

Association of matrix metalloproteinase inducer (EMMPRIN) with the expression of matrix metalloproteinases-1, -2 and -9 during periapical lesion development

Objective

To evaluate the expression of matrix metalloproteinase inducer (EMMPRIN) and its correlation with the expression of matrix metalloproteinases (MMPs)-1, -2 and -9 during the development of periapical lesion in mice.

Methods

Periapical lesions were induced in the lower first molars of mice and after 7, 14, 21 and 42 days the mandibles were removed. The periapical lesions were measured by micro-computed tomography. The expression of EMMPRIN, MMPs-1, -2, and -9 genes were determined by real-time RT-PCR. The location and expression of EMMPRIN and MMPs were evaluated by immunohistochemistry.

Results

At 14 days, the periapical lesion area was higher than at 7 days. At 21 and 42 days no statistically significant bone loss was observed in comparison to 14 days. The control group showed discrete and occasional EMMPRIM, MMP-1, -2 and -9 immunostaining in the periodontal ligament fibroblasts. At 7, 14, 21 and 42 days intense immunoexpression was observed for EMMPRIN, MMPs-1, -2 and -9 in the region adjacent to the apical foramen. The EMMPRIN immunoexpression was higher at 7, 14, 21 and 42 days compared with the control. There was a positive correlation between gene expression of EMMPRIN and MMPs in the active phase of periapical lesion development.

Conclusion

There is a high expression of EMMPRIM mainly by the inflammatory infiltrate in the region adjacent to the apical foramen during periapical lesion development. Furthermore, the positive correlation with MMP-1, -2, and -9 during the first days after periapical lesion induction indicates that EMMPRIM may be involved in the active phase of periapical lesions development.     

Changes in the expression of MMP-3, MMP-9, TIMP-1 and aggrecan in the condylar cartilage of rats induced by experimentally created disordered occlusion

Objective

To investigate the effects of experimentally created disordered occlusion on the mandibular condylar cartilage in terms of histological morphology and expression of MMP-3, MMP-9, TIMP-1 and aggrecan.

Materials and methods

Eighty 8-week-old Sprague-Dawley rats were randomly divided into two experimental (Exp) and two control (Con) groups, with equal sex and number distribution as subgroups. In the Exp group, the disordered occlusion was created by orthodontically moving the first and third molars 0.8 mm away. Hematoxylin-eosin and immunohistochemical staining were performed on the mandibular condyles at the end of the 8th or 12th week. Gene expression was analysed by real-time PCR.

Results

Osteoarthritis-like lesions, typically seen as a cell-free area, were detected in the Exp group, predominantly in females. In the cell-free area, the immunopositive expression of MMP-3, MMP-9, TIMP-1 and aggrecan were absent. Hyper-proliferation changes, typically seen as conjunctive invaginations of chondrocytes, were also observed where immunopositive expression of the tested materials was strong. There were sex and time point related differences in gene expression. In the 8-week subgroup, the expression of MMP-3 decreased, while aggrecan increased in males; however, both MMP-9 and TIMP increased in the female group (P < 0.05). In the 12-week subgroup, the expression of MMP-3 increased, while TIMP, MMP-9 (male only) and aggrecan (female only) decreased (P < 0.05).

Conclusions

The present results indicate that the experimentally created disordered occlusion led to osteoarthritis-like lesions accompanied by changes in the expression of MMP-3, MMP-9, TIMP-1 and aggrecan in mandibular condyle cartilage with gender differences.     

T lymphocyte activation and cytokine expression in periapical granulomas and radicular cysts

Introduction

Radicular cysts (RCs) are periapical lesions resulting in jaw bone destruction. The inflammatory dental periapical granuloma (PG) is considered to be the origin of RC formation; however the mechanism of RC development remains unclear.

Methods

Cell suspension from the surgically extirpated tissue of 27 RCs and 25 PGs was obtained. Bacteriological analysis of the PG tissue samples was performed in order to define two major groups of PG according to the prevailing causative bacterial infection: the streptococcal PG (PG-S, n = 10) and the anaerobe PG (PG-A, n = 9) group. The inflammatory response of tissue infiltrating lymphocytes was assessed by following T lymphocyte activation (HLA-DR expression) as well as interferon γ (IFN-γ) and interleukin 4 (IL-4) production which were evaluated by the flow cytometry.

Results

In comparison to RC both types of PG contained a higher proportion of activated T cells (HLA-DR) and lower proportion of IL-4 producing cells. PG-A tissue contained increased percentage of CD3 cells and increased percentage of T helper 1 (Th1) cells in comparison with PG-S. In RC the IFN-γ production is higher than in streptococcal PG-S but similar as in PG-A.

Discussion

Tissue infiltration by Th2 cells and IL-4 production is likely to play an etiopathogenic role in RC formation.     

Comparison of vehicles to collect dentinal fluid for molecular analysis

Objectives

To test the hypothesis that a material with higher water absorption than polyvinylidene fluoride (PVDF) could increase the yield of target molecules from exposed dentine.

Methods

In a series of standard tests, different cellulose membranes were compared to a PVDF counterpart for their ability to absorb water and release protein. In a subsequent randomized clinical trial, the cellulose material with the most favourable values was compared to PVDF regarding the levels of MMP-2 that could be collected from exposed dentine of healthy human teeth during filling replacement. MMP-2 levels were determined by enzyme-linked immunosorbent assay (ELISA). Data from the laboratory experiments were compared between materials using the appropriate parametric tests. The frequency of cases yielding quantifiable levels of MMP-2 was compared between materials by Fisher's exact test. The level of significance was set at 5%.

Results

The cellulose membrane with the largest pore size (12–15 μm) absorbed significantly (P < 0.05) more water than PVDF. It showed a protein release that was similar to that of PVDF, while the cellulose membranes with smaller pore size retained significantly more protein (P < 0.05). Using the large-pore cellulose membrane, MMP-2 could be collected at a quantifiable level from the dentine of healthy teeth in 9 of 13 cases, compared to 1 of 13 with the PVDF membrane (P < 0.05).

Conclusions

Under the current conditions, a large-pore cellulose membrane yielded more of a molecule of diagnostic value compared to a standard PVDF membrane.

Clinical significance

Molecular diagnostics of dentinal fluid are hampered by low yields. In the current study, it was shown that cellulose membranes are more useful to collect MMP-2 from dentinal fluid than PVDF membranes.     

Do salivary and serum collagenases have a role in an association between obstructive sleep apnea syndrome and periodontal disease? A preliminary case–control study

Objectives

Despite increasing evidence for an association of obstructive sleep apnea syndrome (OSAS) and periodontal disease, the pathophysiological linking mechanisms remain unclear. This study aims to evaluate the salivary and serum matrix metalloproteinase-2, -8, -9 (MMP-2, -8, -9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), myeloperoxidase (MPO), neutrophil elastase (NE), neutrophil gelatinase-associated lipocalin (NGAL), as well as degree of activation of MMP-2, -9 of patients with and without OSAS.

Design

A total of 50 individuals were included in the study. There were 13, 17 and 20 individuals, respectively in the control (non-OSAS) group, mild-to-moderate OSAS and severe OSAS groups. Saliva, serum samples and clinical periodontal parameters were collected. Biofluid samples were analysed by immunofluorometric assay (IFMA), enzyme-linked immunosorbent assay (ELISA), western immunoblotting and gelatine zymography. Statistical analyses were performed using D’Agostino–Pearson omnibus normality test, Kruskal–Wallis test and Spearman rho rank correlation analysis.

Results

There were no statistically significant differences in clinical periodontal parameters between the study groups. Salivary NE and proMMP-2 levels were significantly lower in the OSAS groups than the control group (p < 0.05). Serum proMMP-9 concentration and the degree of MMP-9 activation in saliva were significantly lower in the severe OSAS group than the control group (p < 0.05). There were significant correlations between salivary and serum proMMP-9 and -2 concentrations (p < 0.05). Serum proMMP-2, NE and salivary proMMP-9 and -2 negatively correlated with indicators of OSAS severity (p < 0.05).

Conclusions

The present findings do not support a pathophysiological link between the severity of OSAS and clinical periodontal status via neutrophil enzymes or MMPs.     

Effects of induced periapical abscesses on rat pregnancy outcomes

Objective

The objective of this study was to determine the effects of induced periapical abscesses on pregnant rats.

Design

In 1/2 of the animals (n = 16), the pulps of the maxillary right molars were exposed to the oral environment, which resulted in a periapical abscess. The other 1/2 (n = 16) were sham-operated. 1/2 of the animals of both groups became pregnant 2 weeks later. The pregnancy duration, and weight and number of pups were assessed at delivery. Serum, liver and uterine horn samples were taken from all animals at euthanasia and serum IL-6, endothelin-1, TNF-α, IL-10, cortisol and insulin were determined by ELISA. Liver concentrations of IL-6, CRP and IL-6 and uterine horn concentrations of IL-6, vascular endothelial growth factor (VEGF), TNF-α, IL-10 and IL-1-β were assessed by ELISA. Blood glucose concentrations were determined using a glucometer. Outcome variables were compared by factorial ANOVA, a post hoc Tukey test, and Pearson’s correlation test.

Results

Pregnant rats with periapical abscesses had a significantly longer pregnancy and delivered pups with a significantly higher birthweight (p < 0.05). They had significantly higher concentrations of IL-6, VEGF, IL-1-β, and IL-10 within the uterine horn and IL-6, CRP and TNF-α within the liver (p < 0.01). Blood glucose and serum TNF-α, IL-6, endothelin-1, IL-10, and insulin concentrations were significantly higher in the pregnant animals with pulpal abscesses (p < 0.01).

Conclusion

The significant increase in serum TNF-α, taken together with significant increases in blood glucose and serum insulin concentrations, suggest that animals with induced periapical abscesses developed insulin resistance, which significantly affected their pregnancy outcomes.     

Histologic evaluation and immunohistochemical localization of STRO-1 and BMP-4 in rat immature teeth: A comparison between vital and induced pulp necrosis

Objective

To assess histological features and the expression of STRO-1 and BMP-4 in dental pulp and periapical tissues in vital or necrotic rat immature teeth.

Design

The lower left first molars of male Wistar rats ageing four weeks (n = 24) had their pulps exposed to the oral environment for 3, 6, 9 and 12 weeks (animals ageing 7, 10, 13 and 16 weeks-old, respectively; n = 24). The right lower first molars served as control untouched teeth. After sample harvesting the jaws were dissected and processed for histology and immunodetection of STRO-1 and BMP-4.

Results

Necrotic teeth had root development arrested, while control animals showed development of dental tissues. Immunohistochemistry showed that detection of BMP-4 was restricted to vital pulps. For both groups, STRO-1 expression was evident around blood vessels walls. Neither BMP-4 nor STRO-1 was observed in the apical papilla region.

Conclusion

STRO-1-positive precursor cells were not detected in the apical papilla. BMP-4 expression has not been detected during infection.     

The inhibitory effect of proanthocyanidin on soluble and collagen-bound proteases

Objective

This study evaluated the inhibitory effect of proanthocyanidin (PA), a natural collagen cross-linker, on soluble and matrix-bound proteases, which are responsible for progressive degradation of exposed collagen fibrils within the hybrid layer and resin–dentine bond failure over time.

Methods

The inhibitory effects of PA (1%, 2%, 3%, 4.5% and 6%) on soluble recombinant matrix metalloproteinases (MMP-2, -8 and -9) and cysteine cathepsins (cathepsin B and K) were evaluated using MMP and cysteine cathepsins fluorometric assay kits. Chlorhexidine (CHX) was used as an inhibitor control. The effect of PA on endogenous matrix-bound proteases was examined by determining the change in dry mass of demineralized dentine beams and solubilized collagen peptides over 30 days. Two-way ANOVA and Tukey multiple comparison tests were used to analyze the effect of PA and proteases on the percentage inhibition of soluble proteases (α = 0.05). Kruskal–Wallis one-way ANOVA and Dunn's multiple comparison tests were used to analyse the effect of PA on loss of dry mass and hydroxyproline content over time (α = 0.05).

Results

Proanthocyanidin inactivated more than 90% of soluble recombinant MMP-2, -8 and -9 and around 75–90% of cysteine cathepsin B and K, which was significantly higher than CHX (P < 0.05). The inhibition of endogenous proteases by PA increased in a dose-dependent manner. The loss of dry mass and hydroxyproline release in the medium over time was the lowest in dentine beams pretreated with PA < CHX < control (P < 0.05).

Conclusion

Proanthocyanidin exhibited both dentine MMP and cysteine cathepsins inhibition, which was higher than chlorhexidine.     

Novel missense mutations in the AXIN2 gene associated with non-syndromic oligodontia

Objective

Oligodontia, which is the congenital absence of six or more permanent teeth excluding third molars, may contribute to masticatory dysfunction, speech alteration, aesthetic problems and malocclusion. To date, mutations in EDA, AXIN2, MSX1, PAX9, WNT10A, EDAR, EDARADD, NEMO and KRT 17 are known to associate with non-syndromic oligodontia. The aim of the study was to search for AXIN2 mutations in 96 patients with non-syndromic oligodontia.

Design

We performed mutation analysis of 10 exons of the AXIN2 gene in 96 patients with isolated non-syndromic oligodontia.

Results

We identified two novel missense mutations (Exon 3 c.923C > T and Exon 11 c.2490G > C) in two patients. One mutation (c.923C > T) results in a Thr308Met substitution and the other mutation (c.2490G > C) results in a Met830Ile substitution.

Conclusions

This is the first report indicating that mutations in AXIN2 are responsible for oligodontia in the Chinese population. Our findings indicate that AXIN2 can be regarded as a candidate gene for mutation detection in individuals with non-syndromic oligodontia in the Chinese population.     

Immunohistochemical and biochemical assay of MMP-3 in human dentine

Objective

The function of endogenous MMP-3 and its distribution within the human dentine is unclear. Thus, the aim of the present study was to assay the presence and distribution of MMP-3 within human sound dentine by means of biochemical and immunohistochemical assays.

Methods

Powdered dentine from extracted human teeth was prepared and (1) partially demineralised with 1% H₃PO₄ for 10 min or (2) untreated (control). The presence of MMP-3 was measured using a colorimetric assay system (QuantiSir™, Epigentek, USA). Additional cryo-fractured dentine fragments were processed for immunohistochemical identification of MMP-3 under FEI-SEM. Casein-zymography was used to investigate MMP-3 activity.

Results

MMP-3 detected level was 2.732 ng/μL in partially demineralised dentine powder, whilst it increased to 3.280 ng/μL in mineralised dentine. The FEI-SEM analysis revealed positive immunolabelling patterns for MMP-3, predominantly localized on the intertubular collagen fibrillar network showing MMP-3 directly or indirectly bound to the collagen fibrils. Casein-zymograms showed positive proteolytic activity for MMP-3 in demineralised dentine powder.

Conclusion

The results of the study clearly revealed the presence and distribution of MMP3 in human sound dentine. Whilst the presence was verified, its role is still unclear. Future studies are needed to investigate the possible involvement of MMP-3 in physiological and pathological condition of the dentine-pulp complex.     

Setting kinetics and shrinkage of self-adhesive resin cements depend on cure-mode and temperature

Objective

To investigate the influence of curing mode and temperature on the shrinkage kinetics of self-adhesive resin cements in comparison to a conventional multi-step resin cement.

Methods

The shrinkage of self-adhesive resin cements Maxcem Elite (MX), Speedcem (SPC), Smartcem2 (SMC), iCem (IC) and RelyX Unicem (RX) and Nexus Third Generation (NX3) as a multi-step resin cement was measured continuously for 1 h using the bonded disk method. All materials were tested with dual-curing (dc) and self-curing (sc) mode. All measurements (n = 5 per group) were conducted at room temperature (23 °C) as well as at body temperature (37 °C). Shrinkage time constants were obtained from a simple exponential growth model. Data were statistically analyzed by ANOVA and the p-values were adjusted for multiplicity according to Hothorn et al. (2008) using the R-package “multcomp”.

Results

Shrinkages ranged between 1.84 (RX sc23) and 7.09 (IC sc37). The curing-mode changing from sc to dc had the dominant effect for several materials, especially RX, both on final shrinkage and time constant for setting. Temperature increase had an effect on setting and shrinkage for all materials except RX. Final shrinkage for SPC, SMC and NX3 was statistically equivalent (p > 0.05).

Significance

The 3-fold variation in final shrinkage for these materials is significant for clinical material selection. Light curing can lead to a 10-fold increase in the rate of setting. A self-adhesive universal resin cement (RX) had the lowest shrinkage in the groups examined.     

Influence of gender on the metabolism of alcohols in human saliva in vitro

Objective

The aim of this study was to investigate possible gender differences in salivary metabolism of two alcohols, ethanol and 2-propanol. Ethanol and its metabolite acetaldehyde may play important roles in tumour development, especially in the upper digestive tract. 2-Propanol is tested to elucidate our previous findings, where gender-specific differences in salivary acetone levels were seen after exposure to this alcohol.

Design

Saliva was collected from 25 females and 22 males for in vitro exposure to 2-propanol. In the experiments with ethanol, saliva samples were collected from 17 females and 18 males. The saliva was exposed in vitro to 2-propanol or ethanol. The metabolites acetone, derived from 2-propanol, and acetaldehyde, derived from ethanol, together with the maternal substance were analysed by headspace gas chromatography.

Results

No differences related to gender, age, medication or tobacco intake in the acetone concentration in the saliva samples were found. Gender, age or tobacco intake did not result in difference in the production of acetaldehyde in saliva. However, in the pre-exposure samples the men had a significantly higher concentration of acetaldehyde compared to the women (p = 0.04). Also, there was a tendency (p = 0.05) to higher concentrations of acetaldehyde in the samples (at 1 mM ethanol exposure) from subjects who take medications.

Conclusion

No gender difference in the metabolism of 2-propanol and ethanol in human saliva in vitro were found.     

The effect of low intensity pulsed ultrasound in a 3D ex vivo orthodontic model

Objectives

This study investigated the effects of low intensity pulsed ultrasound (LIPUS) on dentoalveolar structures during orthodontic force application using a novel organ culture system.

Methods

Mandibles were dissected from 28-day-old male Sprague Dawley rats, sliced into 1.5 mm and cultured at 37 °C and 5% CO₂, prior to application of a 50 g force to each mandible slice. Slices were randomly divided into three groups of control, 5 and 10 min LIPUS application and cultured for five days before histological and histomorphometrical analysis.

Results

Cementum and predentine thickness and subodontoblast and periodontal ligament cell counts were increased in the ultrasound groups, with increases statistically significant in the 10 min treated groups. Odontoblasts remained viable during LIPUS exposure and osteoclast activity was increased by LIPUS.

Conclusions

LIPUS may influence remodelling of the dentine-pulp complex and associated tissues during orthodontic force application ex vivo.     

Extracts of irradiated mature human tooth crowns contain MMP-20 protein and activity

Objectives

We recently demonstrated a significant correlation between enamel delamination and tooth-level radiation dose in oral cancer patients. Since radiation can induce the synthesis and activation of matrix metalloproteinases, we hypothesized that irradiated teeth may contain active matrix metalloproteinases.

Materials and methods

Extracted teeth from oral cancer patients treated with radiotherapy and from healthy subjects were compared. Extracted mature third molars from healthy subjects were irradiated in vitro and/or incubated for 0–6 months at 37 °C. All teeth were then pulverized, extracted, and extracts subjected to proteomic and enzymatic analyses.

Results

Screening of irradiated crown extracts using mass spectrometry identified MMP-20 (enamelysin) which is expressed developmentally in dentine and enamel but believed to be removed prior to tooth eruption. MMP-20 was composed of catalytically active forms at Mr = 43, 41, 24 and 22 kDa and was immunolocalized predominantly to the morphological dentine enamel junction. The proportion of different sized MMP-20 forms changed with incubation and irradiation. While the pattern was not altered directly by irradiation of healthy teeth with 70 Gy, subsequent incubation at 37 °C for 3–6 months with or without prior irradiation caused the proportion of Mr = 24–22 kDa MMP-20 bands to increase dramatically. Extracts of teeth from oral cancer patients who received >70 Gy radiation also contained relatively more 24 and 22 kDa MMP-20 than those of healthy age-related teeth.

Conclusion

MMP-20 is a radiation-resistant component of mature tooth crowns enriched in the dentine–enamel. We speculate that MMP-20 catalyzed degradation of organic matrix at this site could lead to enamel delamination associated with oral cancer radiotherapy.     

Influence of saliva substitute films on the initial adhesion of Candida albicans to dental substrata prior to and after artificial ageing

Objective

The aim of this in vitro study was to investigate whether saliva substitute films influence the adhesion of Candida albicans to different dental substrata prior to and after artificial ageing.

Design

Specimens of a denture base resin (DB) and a veneering composite (VC) were polished and subjected to an artificial ageing protocol (thermal cycling, 2 × 3000 cycles 5/55 °C). Bovine enamel (BE) and glass were used as reference materials. After determination of surface free energy, specimens were rinsed with commercial saliva substitutes (Aldiamed, Saliva natura, Saliva Orthana, Salinum), a positive control (protein mixture), or a negative control (Phosphate Buffered Saline, PBS) for 2 h at 37 °C in a flow chamber. Specimens were then exposed to a C. albicans ATCC 10231 suspension for 4 h at 37 °C. Adherent, viable Candida cells were quantified using a luminometric ATP-based assay. Statistical analysis was performed using 1- and 2-way ANOVA, and post-hocs were analysed using the Tukey-Kramer test (α < .05).

Results

Our data indicated that VC (31.1 mJ/m²) and DB (33.9 mJ/m²) yielded the lowest surface free energy prior to artificial ageing, and BE (43.6 mJ/m²) yielded the highest surface free energy. For C. albicans adhesion, both the materials as well as the saliva substitutes influenced relative luminescence intensities, indicating significant differences in C. albicans adhesion between the various materials and after treatment with the saliva substitutes.

Conclusions

Saliva substitutes may have a decisive influence on C. albicans adhesion, but their impact appears to be dependent on the properties of the underlying substratum material.     

Clinical and genetic evaluation of a Chinese family with isolated oligodontia

Objectives

Oligodontia is defined as the congenital absence of 6 or more permanent teeth excluding the third molar. Tooth agenesis may be classified as syndromic/non-syndromic and as familial/sporadic. To date, more than 300 genes have been found to be involved in tooth development, but only a few of these genes, such as MSX1, PAX9 and AXIN2, are related to the condition of non-syndromic oligodontia. The objective of the present work was to investigate the disease-causing gene of non-syndromic oligodontia in a Han Chinese family and analyse the pathogenesis of mutations that result in oligodontia.

Design

We examined all individuals of the oligodontia family by clinical and radiographic examinations. Based on the clinical manifestations, the candidate genes MSX, PAX9 and AXIN2 were selected to analyse and screen for mutations.

Results

The clinical evaluation suggested that the family might show non-syndromic oligodontia. DNA sequencing of the MSX1 gene revealed two mutations in the two patients with oligodontia: a heterozygotic silent mutation, c.348C > T (P.Gly116=), in exon 1 and a homozygotic deletion of 11 nucleotides (c.469 + 56delins GCCGGGTGGGG) in the intron. However, the silent mutation and the deletion mutation were thought to be known polymorphisms (rs34165410 and rs34341187) by bioinformatics analysis. We did not detect any mutations in the PAX9 and AXIN2 genes of oligodontia patients.

Conclusion

Our finding suggests that identified polymorphisms (c.348C > T and c.469 + 56delins GCCGGGTGGGG) may be responsible for the oligodontia phenotype in this Chinese family, but the association requires further study.     

Higher Expression of Galectin-3 and Galectin-9 in Periapical Granulomas than in Radicular Cysts and an Increased Toll-like Receptor-2 and Toll-like Receptor-4 Expression Are Associated with Reactivation of Periapical Inflammation

Introduction

Cysts and periapical granulomas are inflammatory reactions that develop in response to periapical infection by microbial species in dental root canal. It is known that toll-like receptors (TLRs) are pathogen recognition molecules and that galectins are lectins that can be associated with the inflammatory process, stimulating or inhibiting the immune system. The objective of this study was to evaluate the in situ expression of TLRs and galectins in radicular cysts and periapical granulomas.

Methods

We analyzed 62 cases (30 radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR-4) and galectins (Gal-3 and Gal-9).

Results

The expression of Gal-3 and Gal-9 was significantly higher in periapical granulomas and radicular cysts than in the control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more in periapical granulomas than in radicular cysts. The expression of TLR-2 was significantly higher in periapical granulomas and radicular cysts than in the control group, and it was also significantly higher in radicular cysts with sinus tract than in the cases without sinus tract. Furthermore, the expression of TLR-4 was significantly higher in the cases of periapical granulomas with sinus tract than in the cases without sinus tract.

Conclusions

Gal-3/Gal-9 and TLR-2/TLR-4 expression in the periapical granulomas and radicular cysts is associated with reactive periapical inflammation. Pathobiology of periapical disease is a very complex interplay of many bioactive molecules involved in immunoinflammatory responses. Up-regulation of these bioactive molecules might be an important modulator of inflammatory periapical lesions.