Journal of Dental Research

Aggressive periodontitis (AP) in pre-pubertal children is often associated with genetic disorders like Papillon-Lefèvre syndrome (PLS). PLS is caused by mutations in the cathepsin C (CTSC) gene. We report a novel CTSC mutation (c.566-572del) in an otherwise healthy AP child and two novel compound heterozygous mutations (c.947T>G, c.1268G>C) in a PLS patient. We conclude that at least a subset of pre-pubertal AP is due to CTSC mutations and therefore may be an allelic variant of PLS.

Transmission of HIV-1 through the oral cavity is considered to be a rare event. To identify factors in resistance/susceptibility to oral HIV-1 infection, we analyzed expression in human gingiva of HIV-1 receptors Langerin, DC-SIGN, MR, and GalCer, HIV-1 co-receptors CCCR5, CXCR4, and anti-microbial protein α-defensin-1. Our results show that healthy gingiva is infiltrated with cells expressing all HIV-1 receptors tested; however, there are very few CCR5⁺ cells and a complete absence of CXCR4⁺ cells in the lamina propria. In chronic periodontitis (CP), DC-SIGN, MR, CXCR4, and CCR5 increase, but this was accompanied by a ten-fold increase in α-defensin-1 mRNA. The CCR5⁺ cells were revealed to be T-cells, macrophages, and dermal dendritic cells. Moreover, epithelial expression of GalCer and CXCR4 together was not apical and showed no trend with underlying inflammation. Thus, low expression of HIV-1 co-receptors in health and high expression of α-defensin during CP may comprise endogenous factors that provide protection from oral HIV-1 infection.

Mutations in the human amelogenin gene (AMELX, Xp22.3) cause a phenotypically diverse set of inherited enamel malformations. We hypothesize that the effects of specific mutations on amelogenin protein structure and expression will correlate with the enamel phenotype, clarify amelogenin structure/function relationships, and improve the clinical diagnosis of X-linked amelogenesis imperfecta (AI). We have identified two kindreds with X-linked AI and characterized the AMELX mutations underlying their AI phenotypes. The two missense mutations are both in exon 2 and affect the translation initiation codon and/or the secretion of amelogenin (p.M1T and p.W4S), resulting in hypoplastic enamel. Primary anterior teeth from affected females with the p.M1T mutation were characterized by light and scanning electron microscopy. The thin enamel had defective prism organization, and the surface was rough and pitted. Dentin was normal. The severity of the enamel phenotype correlated with the predicted effects of the mutations on amelogenin expression and secretion.

Recently, mast cells have been shown to produce cytokines which can direct the development of T-cell subsets. The aim of the present study was to determine the relationship between mast cells and the Th1/Th2 response in human periodontal disease. Tryptase+ mast cell numbers were decreased in chronic periodontitis tissues compared with healthy/gingivitis lesions. Lower numbers of c-kit+ cells, which remained constant regardless of clinical status, indicate that there may be no increased migration of mast cells into periodontal disease lesions. While there were no differences in IgG2+ or IgG4+ cell numbers in healthy/gingivitis samples, there was an increase in IgG4+ cells compared with IgG2+ cells in periodontitis lesions, numbers increasing with disease severity. This suggests a predominance of Th2 cells in periodontitis, although mast cells may not be the source of Th2-inducing cytokines.

The size of a bolus determines how it will be manipulated in the mouth and swallowed. We hypothesized that mucosal sensitivity would be important for masticatory function. The accuracy of solid object size perception, spatial acuity, and food particle size reduction during mastication were measured in 22 healthy adults with/without topical anesthesia of their oral mucosa. Topical anesthesia had no effect on the perception of sphere sizes, but significantly reduced spatial sensitivity. Without anesthesia, there was a correlation between an individual’s ability to perceive the sizes of steel spheres (diameter, 4–9 mm) and the sizes of food particles chewed for 15 cycles and at swallowing. There was no correlation between spatial sensitivity and food particle size. We suggest that the stimuli used to test two-point discrimination stimulates only superficial receptors, which involve light touch and are easily anesthetized, while the spheres might excite more deeply-set receptors. The latter appear to be more important for masticatory performance and swallowing.

Pilocarpine induces a profuse flow of saliva when administered orally, but effects on drug-induced oral dryness have not been examined. The aim of this trial was to investigate if pilocarpine increases production of saliva in individuals suffering from dry mouth due to treatment with opioids. Sixty-five individuals were enrolled in a randomized, double-blind, placebo-controlled trial. The subjects received tramadol (50 mg t.d.s.) to induce oral dryness, and were thereafter assigned to one of three groups. Secretion rate of saliva was measured before and after tramadol, and after the oral administration of pilocarpine (5 mg), placebo, or no treatment. Baseline characteristics did not differ among the groups (mean ± SEM: 0.37 ± 0.06 mL/min), and tramadol lowered the secretion at the same level in all groups (0.15 ± 0.02 mL/min). Pilocarpine increased the flow above that observed with placebo (0.66 ± 0.19 vs. 0.15 ± 0.02 mL/min). Thus, pilocarpine re-establishes the flow of saliva in the state of tramadol-induced oral dryness.

The efficacy of occlusal splints in diminishing muscle activity and tooth-grinding damage remains controversial. The objective of this study was to compare the efficacy and safety of an occlusal splint (OS) vs. a palatal control device (PCD). Nine subjects with sleep bruxism (SB) participated in this randomized study. Sleep laboratory recordings were made on the second night to establish baseline data. Patients then wore each of the splints in the sleep laboratory for recording nights three and four, two weeks apart, according to a crossover design. A statistically significant reduction in the number of SB episodes per hour (decrease of 41%, p = 0.05) and SB bursts per hour (decrease of 40%, p < 0.05) was observed with the two devices. Both oral devices also showed 50% fewer episodes with grinding noise (p = 0.06). No difference was observed between the devices. Moreover, no changes in respiratory variables were observed. Both devices reduced muscle activity associated with SB.

In synovial joints, friction between articular surfaces leads to shear stress within the cartilaginous tissue, which might result in tissue rupture and failure. Joint friction depends on synovial lubrication of the articular surfaces, which can be altered due to compressive loading. Therefore, we hypothesized that the frictional coefficient of the temporomandibular joint (TMJ) is affected by the magnitude and duration of loading. We tested this by measuring the frictional coefficient in 20 intact porcine TMJs using a pendulum-type friction tester. The mean frictional coefficient was 0.0145 (SD 0.0027) after a constant loading of 50 N during 5 sec. The frictional coefficient increased with the length of the preceding loading duration and exceeded 0.0220 (SD 0.0014) after 1 hr. Application of larger loading (80 N) resulted in significantly larger frictional coefficients. In conclusion, the frictional coefficient in the TMJ was proportional to the magnitude and duration of joint loading.

Root-end filling materials are commonly used following endodontic surgical procedures; however, their effect on adjacent soft tissues is poorly understood. We predict that, due to the differences in their chemical composition, these materials will have profoundly different effects on the survival and differentiation of fibroblasts. Many of the root-end filling materials examined were initially cytotoxic to both PDL and gingival fibroblasts in co-culture experiments; however, this was reduced after the materials were washed in either mineral trioxide aggregate (MTA) or hybrid ionomere composite resin (HICR) for 2 wks. Additionally, PDL fibroblasts displayed enhanced proliferation on MTA and survival on amalgam when compared with gingival fibroblasts. MTA preferentially induced alkaline phosphatase expression and activity in both PDL and gingival fibroblasts. In contrast, HICR inhibited alkaline phosphatase expression and activity. In addition, MTA and HICR repressed pleiotrophin in PDL fibroblasts, while HICR repressed periostin in both fibroblasts. Thus, root-end filling materials differentially affect periodontal fibroblast differentiation. Abbreviations: mineral trioxide aggregate (MTA), zinc-oxide eugenol cement (ZOEC), hybrid ionomer composite resin (HICR), reverse-transcriptase polymerase chain-reaction (RT-PCR).

Endodontically treated teeth restored with posts are susceptible to coronal leakage after long-term function. We hypothesize that demineralized collagen matrices (DCMs) created in dentin by acidic zinc phosphate cement within the dowel spaces degrade with time. Forty-two post-restored teeth were extracted after three periods of clinical service and were examined, by means of scanning and transmission electron microscopy, for the status of the DCMs. SEM revealed a progressive degradation of the DCMs, becoming less dense after 3 to 5 years, losing structural integrity after 6 to 9 years, and partially disappearing after 10 to 12 years. TEM revealed evidence of collagenolytic activity within the DCMs, with loss of cross-banding and unraveling into microfibrils, and gelatinolytic activity that resulted in disintegration of the microfibrils. Bacterial colonization and the release of bacterial enzymes and of host-derived matrix metalloproteinases may contribute to the degradation of collagen fibrils in root dentin after clinical function.

The higher microtensile bond strength values found for specimens with a smaller cross-sectional area are often explained by the lower occurrence of internal defects and surface flaws. We hypothesized that this aberrant behavior is mainly caused by the lateral way of attachment of the specimens to the testing device, which makes the strength dependent on the thickness. This study showed that composite bars of 1×1×10, 1×2×10, and 1×3×10mm attached at their 1-mm-wide side (situation A) fractured at loads of the same magnitude, as a result of which the microtensile strength (μTS), calculated as F/A (force at fracture/cross-sectional area), significantly increased for specimens with decreasing thickness. Attachment at the 1-, 2-, or 3-mm-wide side (situation B) resulted in equal μTS values (P > 0.05). Finite element analysis showed different stress patterns for situation A, but comparable patterns for situation B. Both situations showed the same maximum stress at fracture.

Calcium hydroxide cements can lack long-term stability and achieve sustained release by matrix-controlled diffusion of hydroxyl ions. Tetracalcium phosphate (TTCP) hydrolyzes slowly to form calcium hydroxide and a thin insoluble apatite layer that prevents further reaction. In this study, mechanical amorphization was used to create a setting calcium-hydroxide-releasing cement from TTCP. The effect of high-energy ball milling of TTCP on the mechanical properties of the cement was investigated. X-ray diffraction data were used to determine the phase composition of the set cements. An accelerated in vitro test compared pH of water after prolonged boiling of nanocrystalline TTCP cements and a calcium salicylate material. As milling time increased, cement compressive strength and degree of conversion increased. Hydroxyl ion release from the cement was comparable with that from a calcium salicylate material. This new cement system offers the antimicrobial potential of calcium salicylate materials combined with the long-term stability of insoluble apatite cements.

The periodontal pathogen Porphyromonas gingivalis (Pg) is a potent inducer of the production of pro-inflammatory cytokines by neutrophils, monocytes, and macrophages, and can desensitize immune cells in vitro and in vivo. We analyzed the ability of Pg lipopolysaccharide (LPS) to induce endotoxin tolerance. Treatment of dendritic cells (DC), the human macrophage cell line THP-1, and monocytes (antigen-presenting cells, APC) with Pg.LPS inhibited APC maturation assessed by CD80 and CD86 expression, and inhibited chemokine (CCL3 and CCL5) production. Pre-treatment with glucocorticoids (GC) and interleukin-10 (IL-10) abolished the effect of Pg.LPS on CD80, CD83, and CD86, and on CCL3 and CCL5 production. We also showed that Pg.LPS enhanced the tolerogenic properties of APCs and up-regulated ILT-3 and B7-H1 expression.

Indian hedgehog (Ihh) is a critical mediator transducing mechanical signals to stimulate chondrocyte proliferation. To clarify the cellular signal transduction pathway that senses and converts mechanical signals into tissue growth in mandibular condyle, we evaluated Ihh expression and its relation to the kinetics of replicating mesenchymal cells in condylar cartilage during natural growth and mandibular advancement. Thirty-five-day-old Sprague-Dawley rats were fitted with functional appliances. Experimental animals with matched controls were doubly labeled with iododeoxyuridine and bromodeoxyuridine so that we could evaluate the cycles of the proliferative mesenchymal cells. Mandibular advancement triggered Ihh expression in condylar cartilage. A higher level of Ihh expression coincided with the increase of the replicating mesenchymal cells’ population and the shortening of the turnover time. These findings suggested that Ihh acts as a mediator of mechanotransduction that converts mechanical signals resulting from anterior mandibular displacement to stimulate cellular proliferation in condylar cartilage.