Orthodontic tooth movement is accompanied by inflammatory responses in the periodontal ligament. Chemical mediators such as interleukin-1β have key roles in nociception around teeth. Such nociceptive inputs to the periodontal ligament continue for several days and potentially induce plastic changes in higher brain regions, including the cerebral cortex. This review summarizes research on orthodontic treatment-induced modulation of neural activities in the central nervous system. Furthermore, we describe our recent findings on the spatiotemporal effects of orthodontic treatment in the somatosensory and insular cortices.

Excitability of neurons in the trigeminal ganglion (TG), trigeminal spinal subnucleus caudalis (Vc), and upper cervical spinal cord (C1-C2) is greatly enhanced after orofacial inflammation and trigeminal nerve injury, and TG, Vc, and C1-C2 neurons remain sensitized long after such episodes. Sensitized neurons generate various molecules, which are released from nociceptive neurons in these areas and are involved in modulating the excitability of TG, Vc, and C1-C2 nociceptive neurons. Hyperexcitable nociceptive neurons also activate satellite glial cells in the TG and microglial cells and astrocytes in the Vc and C1-C2. Glial cell activation spreads throughout the TG, Vc, and C1-C2 and triggers the release of various molecules involved in modulating nociceptive neurons in TG, Vc, and C1-C2 neurons. These findings suggest that functional interaction between neurons and glial cells is critical in persistent orofacial pain associated with orofacial inflammation and trigeminal nerve injury.

Neurons in the trigeminal mesencephalic nucleus (Vmes) receive deep sensation (proprioception) from jaw-closing muscle spindles and periodontal ligaments and project primarily to the jaw-closing motoneuron pool (jaw-closing nucleus) of the trigeminal motor nucleus and to the supratrigeminal nucleus. Numerous articles have described the morphology and physiology of the central projections of Vmes afferents originating from the muscle spindles and periodontal ligaments. However, no report has provided a detailed description of projection and synaptic connectivity, especially of single afferents, and their functional implications. In this review, we reanalyze data obtained by single intra-axonal recording and labeling of functionally identified Vmes muscle spindle afferents and periodontal ligament afferents and by electron microscopic observation of their projection features and synaptic organization of boutons, to compare the data for the jaw-closing nucleus and supratrigeminal nucleus. Our analysis shows that each Vmes afferent type has characteristic projection pattern and synaptic feature that may be important in jaw-reflex control.

The tongue can move freely and is important in oral motor functions. Tongue movement must be coordinated with movement of the hyoid, mandible, and pharyngeal wall, to which it is attached. Our previous study using isolated brainstem-spinal cord preparations showed that application of N-methyl-D-aspartate induces rhythmic activity in the hypoglossal nerve that is coincident with rhythmic activity in the ipsilateral trigeminal motor nerve. Partial or complete midline transection of the preparation only abolishes activity in the trigeminal motor nerve; therefore, the neuronal network contributing to coordinated activity of the jaw/tongue muscles is located on both sides of the preparation and sends motor commands to contralateral trigeminal motoneurons. Arterially perfused decerebrate rat preparations exhibit stable inspiratory activity in the phrenic nerve, with efferent nerves innervating the upper airway muscles (the hypoglossal nerve, a branch of the cervical spinal nerve, the external branch of the superior laryngeal nerve, and the recurrent laryngeal nerve) under normocapnic conditions (5% CO₂). During hypercapnia (8% CO₂), pre-inspiratory discharges appear in all nerves innervating upper airway muscles. Such coordinated activity in the pre-inspiratory phase contributes to dilation of the upper airway and improves hypercapnia.

The oral cavity is the first line of defense, sensation, and secretion of the alimentary canal. Oral perception contributes to the enjoyment of food and beverages and to avoiding consumption of poisonous or harmful substances. Oral sensation is served by somatosensory nervous systems distributed to the oral membrane. Recent studies reported that oral epithelial cells may transduce temperature and touch through membranous sensors, which comprise ion channels with multimodal properties, and nerves. Here, we describe the possible role of oral epithelial cells in oral perception.

The nucleus accumbens is a terminal area of the mesolimbic dopaminergic system that arises in the ventral tegmental area. Opioids are thought to enhance dopaminergic activity in the nucleus accumbens by activating δ- and μ-opioid receptors in the ventral tegmental area. However, δ- and μ-opioid receptor agonists increase extracellular levels of accumbal dopamine when infused directly into the nucleus accumbens of rats. Therefore, the roles of δ- and μ-opioid receptors in regulation of accumbal dopaminergic neural activity have been analyzed by using δ- and μ-opioid receptor ligands. This review describes the mechanisms underlying the stimulatory effects on accumbal dopamine efflux, which are induced by local administration of δ- and μ-opioid receptor agonists into the nucleus accumbens of freely moving rats. The focus of this article is neurochemical studies that use in vivo microdialysis techniques. Taken together, the in vivo neurochemical evidence from these studies indicates that δ- and μ-opioid receptor agonists increase accumbal dopamine efflux by activating naloxone-sensitive opioid receptors, and by mechanisms independent of naloxone-sensitive opioid receptors, in the nucleus accumbens.

In this brief review, we discuss our previous research on the relationship between the bacterial composition of salivary microbiota and periodontal disease. Analysis using a terminal restriction fragment length polymorphism method and an international comparison suggest that the predominance of the genera Prevotella and Veillonella in the salivary microbiota is attributable to periodontal disease conditions, and that the predominance of the genus Neisseria indicates healthy periodontal conditions. Furthermore, we recently used next-generation sequencing technology to perform a detailed large-scale analysis of the salivary microbiota. An important finding of that study was that high bacterial richness in the salivary microbiota was significantly associated with poor oral health, as indicated by decayed teeth, periodontitis, and poor oral hygiene. Another important result was that relative abundance of predominant bacteria in saliva was significantly associated with oral health-related conditions. Of the two different cohabiting groups of bacteria found in the salivary microbiota, a greater relative abundance of group I bacteria, which include Prevotella and Veillonella species, was associated with poor oral health, high body mass index, and old age. These findings suggest that the salivary microbiota reflects oral and systemic conditions.

Age-related deterioration in physical and oral health reduces healthy life expectancy and is thus an important problem for very elderly people. We investigated the effects of satisfaction with dietary life (SDL) in everyday life on oral health-related quality of life (OHRQoL) and subjective well-being and examined associations between these factors. We evaluated 426 elders aged 85 years or older. All participants completed a questionnaire that inquired about age, gender, drinking status, body mass index, cognitive function, disability, and comorbidities, among other covariates. Oral, physical, and mental health conditions were also examined. Associations of questionnaire results for SDL with items on subjective well-being (Philadelphia Geriatric Center Morale Scale [PGC] and World Health Organization-5 [WHO-5]) and OHRQoL (Geriatric Oral Health Assessment Index [GOHAI]) were confirmed with multiple logistic regression analysis. In a multivariate model adjusted for various confounders, participants with self-reported “enjoyable” SDL had significantly lower risks for having the lowest scores on the GOHAI, PGC, and WHO-5 (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.277-0.762; OR = 0.589, 95% CI = 0.348-0.996; and OR = 0.452, 95% CI = 0.263-0.775, respectively). These associations remained after further adjustment for number of teeth.

Vasculogenesis is a pivotal procedure during dental implant osseointegration and bone repair process. Vascular endothelial growth factor (VEGF), regarded as one of the most important vasculogenesis factor, also plays a central role in bone repair, but its role around dental implants is still unknown. In the present study, rat primary osteoblasts seeded on titanium discs were tested using proliferation, enzyme-linked immunosorbent assay, Real-time PCR, and alkaline phosphatase (ALP) expression. Chicken embryo chorioallantoic membrane (CAM) was used to test the vasculogenesis property. In vivo VEGF-coated implants assay was used to test the osteocalcin (OCN)- and CD31-positive cells around an implant. VEGF could significantly promote osteoblasts seeded on titanium surfaces proliferation and secretion of VEGF protein (P < 0.05); increasing of VEGF, VEGFR1, VEGFR2, NRP-1, ALP and Runx2 mRNA expression (P < 0.05); up-regulating ALP expression on days 7 and 11 (P < 0.01). Supernatant of VEGF-induced osteoblasts could promote CAM vasculogenesis (P < 0.05). In vivo, VEGF-coated implants could promote OCN- and CD31-positive cells around bone lacunas. The present study shows that VEGF could induce primary rat osteoblasts proliferation, VEGF protein secretion, ALP expression, and VEGF-related mRNA expression in vitro. Osteoblasts co-cultured with VEGF could promote neovascularization in chicken embryos. In the in vivo experiments, coating the implant with VEGF could promote osteoblasts and endothelial cell expression.

The aim of this study was to evaluate in vivo bone regeneration, mediated by adipose-derived stem cells (ADSCs), induced to differentiate into osteoblasts and carried by a scaffold gel. In the test group, bone regeneration was mediated by ADSCs, induced to differentiate into osteoblasts, and carried by a scaffold gel. In the control group a scaffold without cells was used. The scaffold, consisting of chitosan and glycerol phosphate, was maintained in situ by a cross-linked resorbable membrane. The osteogenic potential of ADSCs was confirmed by osteocalcin assay and Von Kossa staining performed before implantation. Histological assays detected an initial increase in bone formation in the test group compared with the control group. Microcomputed tomography analysis did not show significant differences between the two groups. Both histological and microcomputed tomography analysis were performed on the ex vivo specimens after a follow-up period of 8 weeks. We observed that differentiated ADSCs could increase bone regeneration and that the scaffold used here can be a suitable carrier to entrap and maintain the cells in situ. On the contrary, the membrane used was not functional in isolating the site of the defect from surrounding soft tissues and caused a significant inflammatory reaction.

This study evaluated the intraexaminer repeatability of measurements of surface electromyography (EMG) variables and functional indices of the myoelectric signals from the masseter and temporalis muscles bilaterally in 15 healthy men. The test was repeated on two different days without templates. The resting muscle activity was recorded once, and two kinds of maximum voluntary contraction (MVC) tasks were performed and recorded three times. The two MVC tasks involved clenching the teeth and biting down on two cotton rolls bilaterally with the posterior teeth. The intraclass correlation coefficient (ICC) of amplitude was >88% and that of frequency was >95% during the two MVC tasks but not under resting conditions. The ICC of the asymmetry and activity indices during the two MVC tasks was >76%. A Bland-Altman analysis revealed no significant difference in amplitude or frequency or in the two indices between the two days during the MVC tasks. In conclusion, the measurements of surface EMG variables and the indices obtained according to the study protocol were highly repeatable in healthy men. Additional studies using templates and intraexaminer measurement errors are warranted in both men and women for complete validation of these findings.

The effects of systemically administered rosuvastatin on alveolar bone loss (ABL), cytokine levels and oxidative status were investigated in rats with ligature-induced periodontitis. Rats were divided randomly into four groups: a non-ligated group (C); a non-ligated+rosuvastatin group (R); a ligated group (P); and a ligated+rosuvastatin group (PR). Ligatures were placed at the maxillary second molars, and rosuvastatin was administered for 14 days. After the rats had been euthanatized, histomorphometric and histological analyses were performed, and the serum levels of interleukin (IL)-1β, IL-10 and oxidant and antioxidant parameters (malondialdehyde [MDA], superoxide dismutase, glutathione, and glutathione peroxidase) were evaluted by enzyme-linked immunosorbent assay. Rosuvastatin significantly decreased the extent of ABL, inflammatory infiltration and osteoclasts in periodontitis, but increased the numbers of osteoblasts. Although rosuvastatin reduced the levels of IL-1β, they did not differ significantly between the PR and P groups. In the PR group, not only were IL-10 levels significantly higher but also the ratio of IL-1β to IL-10 was lower than in the P group. Although MDA levels were significantly increased in the P group relative to the C group, they did not differ significantly between the PR and C groups. The present data suggest that rosuvastatin decreases ABL in ligature-induced periodontitis, and that its anti-inflammatory effect is more remarkable than its antioxidant effect.

This study investigated guidelines for placement of monocortical screws in the mandible, particularly the mandibular canal. In this study of 35 patients, we used cone-beam computed tomography to determine the distance from the alveolar crest to the superior border of the mandibular canal (DMC) and the shortest distance from the buccal and lingual cortex to the mandibular canal (attaining distance) in the areas between premolars (premolar area), between the second premolar and first molar (middle area), and between the first and second molars (molar area). The DMC values for these areas were 16.55, 18.94, and 16.58 mm, respectively, and were similar in adults and adolescents. When the attaining distance was 8 mm, the heights on the buccal and lingual sides of the areas were 9 and 16.6 mm, 13.7 and 14.7 mm, and 15.3 and 12 mm, respectively. Risk of proximity to the mandibular canal should be considered at above heights or greater when an orthodontic anchorage device (OAD) 8 mm in length is placed. Careful attention is needed for placements on lingual side in adolescents. By reducing the OAD length to 6 mm, placement safety increases in all areas except the premolar area, especially on the buccal side.

Fissure sealant retention is traditionally considered as a proxy measure for caries prevention. This study investigated the logic behind this proposition, and its validity. A logical framework of the proposition was established. The mechanism of caries development was transferred into a Directed acyclic graph, and this was used to investigate the logical framework. The sensitivity and specificity of full sealant retention in the prediction of dental carious lesion development and the number of false positive/false negative prediction rates were computed. The sensitivity/specificity was statistically compared to that of random values. A contradiction in the logical framework was identified. The mean sensitivity/specificity was 37.9% (SD = 27.8%) and 67.6% (SD = 28.4%), respectively. When these values were compared against random values (30.5%, SD = 25.7% and 58.7%, SD = 31.6%), a non-significant sensitivity (P = 0.06) and a borderline higher specificity (P = 0.04) were observed. The overall false prediction rate was 33.7%, with 16.9% and 16.8% false negative and false positive predictions, respectively. The sensitivity/specificity was too low and the false prediction rate was too high to consider retention a valid proxy for caries prevention. The logic behind the investigated proposition is flawed, contradicted by the current empirical evidence, and thus invalid.

Previous finite element analyses of peri-implant stress assumed a bone-implant contact (BIC) ratio of 100%, even though the BIC ratio is known to be approximately 50% or less. However, the recent development of ultraviolet treatment of titanium immediately before use, known as photofunctionalization, significantly increased the BIC ratio, to 98.2%. We used a unique finite element analysis model that enabled us to examine the effects of different BIC ratios on peri-implant stress. A three-dimensional model was constructed under conditions of vertical or oblique loading, an implant diameter of 3.3, 3.75, or 5.0 mm, and a BIC ratio of 53.0% or 98.2%. Photofunctionalization and larger implant diameters were associated with reduced stress on surrounding tissues. Under vertical loading, photofunctionalization had a greater effect than increased implant diameter on stress reduction. Under oblique loading, increased implant diameter had a greater effect than photofunctionalization on stress reduction.

Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor whose expression level is positively correlated with tumor aggressiveness and metastatic potential. However, the mechanism underlying SLPI-induced enhancement of malignant phenotype is not completely understood. The malignancy of cancer cells is highly dependent on cell migration activity. Our previous study revealed that gingival carcinoma Ca9-22 cells, but not colorectal adenocarcinoma HT-29 cells, expressed SLPI. Therefore, we investigated the migration activity of these two cell types to understand the nature of SLPI-mediated tumor aggressiveness and metastatic potential. In vitro wound healing assay indicated that HT-29 cells and SLPI-deleted Ca9-22 cells showed lower migration activity than wild-type Ca9-22 cells, suggesting that SLPI-induced cell migration plays an important role in tumor aggressiveness and metastatic potential. In addition, our gene expression profiling study based on microarray data for the three cell types identified a number of candidates, including LCP1 and GLI, that could be key molecules in the mechanism of SLPI-induced cell migration.

We investigated human leukocyte antigen (HLA) profiles for Tunisians with nasopharyngeal carcinoma (NPC), their families, and a sample of unrelated healthy Tunisians in order to identify HLA specificities associated with familial NPC. HLA-A, -B, and -DRB1 typing was successful for 36 NPC patients, 72 unaffected family members, and 130 community controls, and the chi square or Fisher exact test was used to compare allele frequencies between cases and controls. We observed a consistent protective effect of HLA-DRB1*10 on NPC development. However, none of the NPC patients or their family members had a positive result for this HLA marker (0% vs 9.2% in controls, P = 0.047). In addition, HLA-A*26 was probably an induction marker, as its allelic frequency was significantly higher among NPC patients than among controls (P = 0.003) and among NPC patients than among at-risk family members (P = 0.067). Logistic regression analysis of the joint effect of selected HLA specificities showed that HLA-A*26 and HLA-A*30 were co-associated and have an important effect on NPC risk. Despite the small size of our cohort, we showed that HLA-A*26-A*30 and HLA-DRB1*10 might be predictive markers for NPC screening of Tunisian families with a high risk of NPC.

Asthma is a chronic inflammatory disease, and its prevalence is relatively high among children. Optimal management of asthma often requires long-term pharmacotherapy; however, the effects of these medications on orthodontic treatment is uncertain. We evaluated the effects of the leukotriene LTD₄ receptor antagonist montelukast on orthodontic tooth movement in an animal model. Eight mongrel dogs were given montelukast for periods up to 4 weeks. An orthodontic force of 150-200 g was applied to move the second and fourth premolars toward the site of the extracted third premolar. The distance between premolars was measured at baseline and at weeks 1, 2, and 4. Histological examination with hematoxylin-eosin staining was used to evaluate osteoclast activity. A slight delay in orthodontic movement and decreased osteoclast activity were observed in the montelukast-treated group, as compared with untreated controls. However, the differences were not statistically significant (P > 0.05). Our findings suggest that montelukast use will not interfere with orthodontic treatment of asthma patients. However, these findings require confirmation in clinical studies.

Periodontal disease is caused by inflammation induced by Porphyromonas gingivalis (P.g.) lipopolysaccharide (LPS) and involves expression of proinflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-α, and receptor activator of nuclear factor kappa B ligand (RANKL), which are implicated in bone resorption. Low-intensity pulsed ultrasound (LIPUS) is commonly used in the treatment of bone fracture. However, the mechanisms by which LIPUS inhibits LPS-induced inflammatory cytokines are poorly understood. Therefore, we investigated the effects of LIPUS on LPS-induced expression of the proinflammatory cytokines IL-6 and RANKL. MC3T3-E1 cells were incubated in the presence or absence of P.g. LPS and then stimulated with LIPUS for 30 min/day for a maximum of 14 days. LPS increased mRNA and protein expressions of IL-6 and RANKL on day 14. In addition, mRNA expression of COX-2 LPS was higher after 3 and 7 days of LIPUS treatment. PGE₂ was induced by LPS after 7 and 14 days of culture. LIPUS suppressed all stimulatory effects of LPS. These results suggest that LIPUS inhibits LPS-induced expression of inflammation cytokines by suppressing PGE₂ production and might thus have potential applications in the treatment of periodontitis.

This clinical report describes the use of biological tissue adaptation technique for placement of a porcelain laminate veneer in a 50-year-old woman. The author developed this prosthetic technique to facilitate alignment of gingival levels for esthetic purposes. The laminate veneer was seated on the maxillary central incisor with an adhesive system. Although the margin of the restoration overhangs, no gingival inflammation or recession has been observed during a follow-up period of 10 years and 9 months.