Association Between Reduced Posterior Occlusal Contact and Alzheimer's Disease Onset in Older Japanese Adults: Results from the LIFE Study.

BACKGROUND: An association between poor oral health and cognitive decline has been reported. Most of these studies have considered the number of teeth as a criterion, only a few studies have analyzed the relationship between occlusal status and Alzheimer's disease (AD). OBJECTIVE: To elucidate whether posterior occlusal contact is associated with AD, focusing on the Eichner classification, among an older population aged 65 years or older in Japan. METHODS: This study used monthly claims data of National Health Insurance in Japan from April 2017 to March 2020. The outcome was newly diagnosed AD defined according to ICD-10 code G30. The number of teeth was estimated by dental code data, and occlusal contact was divided into three categories, namely A, B, and C, according to the Eichner classification. Multivariate Cox proportional hazards models were used to analyze the association between a new diagnosis of AD and the Eichner classification. RESULTS: A total of 22,687 participants were included, 560 of whom had newly diagnosed AD during a mean follow-up period of 12.2 months. The AD participants had a lower proportion of Eichner A and a higher proportion of Eichner C. After adjusting for covariates, hazard ratios (95% confidence intervals) with Eichner B and C were 1.34 (1.01-1.77) and 1.54 (1.03-2.30), respectively. CONCLUSION: In older people aged≥65 years old, reduced posterior occlusal contact as well as tooth loss have an impact on AD. This study emphasizes the importance of paying attention to occlusal contacts to reduce the risk of AD.

Identification of GPI-anchored protein LYPD1 as an essential factor for odontoblast differentiation in tooth development.

Lipid rafts are membrane microdomains rich in cholesterol, sphingolipids, glycosylphosphatidylinositol-anchored proteins (GPI-APs), and receptors. These lipid raft components are localized at the plasma membrane and are essential for signal transmission and organogenesis. However, few reports have been published on the specific effects of lipid rafts on tooth development. Using microarray and single-cell RNA sequencing methods, we found that a GPI-AP, lymphocyte antigen-6/Plaur domain-containing 1 (Lypd1), was specifically expressed in preodontoblasts. Depletion of Lypd1 in tooth germ using an ex vivo organ culture system and in mouse dental pulp (mDP) cells resulted in the inhibition of odontoblast differentiation. Activation of bone morphogenetic protein (BMP) signaling by BMP2 treatment in mDP cells promoted odontoblast differentiation via phosphorylation of Smad1/5/8, while this BMP2-mediated odontoblast differentiation was inhibited by depletion of Lypd1. Furthermore, we created a deletion construct of the C terminus containing the omega site in LYPD1; this site is necessary for localizing GPI-APs to the plasma membrane and lipid rafts. We identified that this site is essential for odontoblast differentiation and morphological change of mDP cells. These findings demonstrated that LYPD1 is a novel marker of preodontoblasts in the developing tooth; in addition, they suggest that LYPD1 is important for tooth development and that it plays a pivotal role in odontoblast differentiation by regulating Smad1/5/8 phosphorylation through its effect as a GPI-AP in lipid rafts.

Cynomolgus macaque model of neuronal ceroid lipofuscinosis type 2 disease.

Neuronal ceroid lipofuscinoses (NCLs) are autosomal-recessive fatal neurodegenerative diseases that occur in children and young adults, with symptoms including ataxia, seizures and visual impairment. We report the discovery of cynomolgus macaques carrying the CLN2/TPP1 variant and our analysis of whether the macaques could be a new non-human primate model for NCL type 2 (CLN2) disease. Three cynomolgus macaques presented progressive neuronal clinical symptoms such as limb tremors and gait disturbance after about 2 years of age. Morphological analyses using brain MRI at the endpoint of approximately 3 years of age revealed marked cerebellar and cerebral atrophy of the gray matter, with sulcus dilation, gyrus thinning, and ventricular enlargement. Histopathological analyses of three affected macaques revealed severe neuronal loss and degeneration in the cerebellar and cerebral cortices, accompanied by glial activation and/or changes in axonal morphology. Neurons observed throughout the central nervous system contained autofluorescent cytoplasmic pigments, which were identified as ceroid-lipofuscin based on staining properties, and the cerebral cortex examined by transmission electron microscopy had curvilinear profiles, the typical ultrastructural pattern of CLN2. These findings are commonly observed in all forms of NCL. DNA sequencing analysis identified a homozygous single-base deletion (c.42delC) of the CLN2/TPP1 gene, resulting in a frameshifted premature stop codon. Immunohistochemical analysis showed that tissue from the affected macaques lacked a detectable signal against TPP1, the product of the CLN2/TPP1 gene. Analysis for transmission of the CLN2/TPP1 mutated gene revealed that 47 (49.5%) and 48 (50.5%) of the 95 individuals genotyped in the CLN2-affected macaque family were heterozygous carriers and homozygous wild-type individuals, respectively. Thus, we identified cynomolgus macaques as a non-human primate model of CLN2 disease. The CLN2 macaques reported here could become a useful resource for research and the development of drugs and methods for treating CLN2 disease, which involves severe symptoms in humans.

Development of a novel ex vivo organ culture system to improve preservation methods of regenerative tissues.

Recent advances in regenerative technology have made the regeneration of various organs using pluripotent stem cells possible. However, a simpler screening method for evaluating regenerated organs is required to apply this technology to clinical regenerative medicine in the future. We have developed a simple evaluation method using a mouse tooth germ culture model of organs formed by epithelial-mesenchymal interactions. In this study, we successfully established a simple method that controls tissue development in a temperature-dependent manner using a mouse tooth germ ex vivo culture model. We observed that the development of the cultured tooth germ could be delayed by low-temperature culture and resumed by the subsequent culture at 37 °C. Furthermore, the optimal temperature for the long-term preservation of tooth germ was 25 °C, a subnormothermic temperature that maintains the expression of stem cell markers. We also found that subnormothermic temperature induces the expression of cold shock proteins, such as cold-inducible RNA-binding protein, RNA-binding motif protein 3, and serine and arginine rich splicing factor 5. This study provides a simple screening method to help establish the development of regenerative tissue technology using a tooth organ culture model. Our findings may be potentially useful for making advances in the field of regenerative medicine.

Analysis for Predictors of Failure of Orthodontic Mini-implant Using Patient-Specific Finite Element Models.

In this study, we analyzed the clinical factors and mechanical parameters for predicting orthodontic mini-implant (OMI) failure in the mandible, which has different properties from the maxilla. A patient-specific finite element analysis was applied to 32 OMIs (6 failures and 26 successes) implanted between the mandibular second premolars and first molars used for anchorage. The peak stress and strain parameters were calculated for each sample. A logistic regression of the failure (vs. success) of OMIs on the mechanical parameters in the models was conducted. In addition, the influence of clinical factors on the mechanical parameters considered to be related to OMI failure was examined by a regression analysis. The mechanical parameter which best predicts OMI failure in the mandible was found to be a minimum principal strain of between 0.5 to 1.0 mm from the OMI surface (R2 = 0.8033). The results indicate the patient's bone density, distance between the OMIs and adjacent root, and vertical implantation angle of the OMIs are potential clinical predictors of OMI failure in the mandible.

Observational study investigating the relationship between maxillomandibular characteristics and temporomandibular disc conditions in female patients with a skeletal class III pattern.

OBJECTIVES: The objective of this study was to analyze the relationship between maxillomandibular characteristics and the severity of temporomandibular disc displacement in female patients with a skeletal class III (SKIII) pattern. METHODS: Fifty-seven samples were included in the study. The evaluation of articular disc conditions was conducted using magnetic resonance imaging, while 25 cephalometric variables from lateral and postero-anterior (P-A) cephalograms were measured to determine their maxillomandibular characteristics. The samples were categorized into three groups based on the articular disc conditions: (1) normal disc position (NDP), (2) disc displacement with reduction (DDwR), and (3) disc displacement without reduction (DDwoR). The relationship between the maxillomandibular characteristics and disc conditions was examined through both basic statistical analysis and multivariate analysis using principal component analysis (PCA). RESULTS: The Kruskal-Wallis and Dunn-Bonferroni tests revealed a significant difference between the groups in terms of the deviation of mandibular characteristics observed on the P-A cephalogram. The DDwoR group exhibited significantly larger menton deviation, ramal height asymmetry index, and total mandibular length asymmetry index compared to the NDP and DDwR groups. Moreover, the PCA successfully extracted all cephalometric variables into eight principal components. Among them, only the principal component related to mandibular asymmetry was able to differentiate the SKIII samples with DDwoR from the other groups. CONCLUSIONS: The findings of this study highlight a significant relationship between mandibular asymmetry and the severity of disc displacement, particularly DDwoR, in female patients with a SKIII pattern.

Cellular mechanisms of taste disturbance induced by the non-steroidal anti-inflammatory drug, diclofenac, in mice.

Drug-induced taste disorders are a serious problem in an aging society. This study investigated the mechanisms underlying taste disturbances induced by diclofenac, a non-steroidal anti-inflammatory drug that reduces pain and inflammation by inhibiting the synthesis of prostaglandins by cyclooxygenase enzymes (COX-1 and COX-2). RT-PCR analyses demonstrated the expression of genes encoding arachidonic acid pathway components such as COX-1, COX-2 and prostaglandin synthases in a subset of mouse taste bud cells. Double-staining immunohistochemistry revealed that COX-1 and cytosolic prostaglandin E synthase (cPGES) were co-expressed with taste receptor type-1 member-3 (T1R3), a sweet/umami receptor component, or gustducin, a bitter/sweet/umami-related G protein, in a subset of taste bud cells. Long-term administration of diclofenac reduced the expression of genes encoding COX-1, gustducin and cPGES in mouse taste buds and suppressed both the behavioral and taste nerve responses to sweet and umami taste stimuli but not to other tastants. Furthermore, diclofenac also suppressed the responses of both mouse and human sweet taste receptors (T1R2/T1R3, expressed in HEK293 cells) to sweet taste stimuli. These results suggest that diclofenac may suppress the activation of sweet and umami taste cells acutely via a direct action on T1R2/T1R3 and chronically via inhibition of the COX/prostaglandin synthase pathway inducing down-regulated expression of sweet/umami responsive components. This dual inhibition mechanism may underlie diclofenac-induced taste alterations in humans.

Quality of life in preadolescent orthodontic patients before and after secondary alveolar bone grafting.

INTRODUCTION: We evaluated the effects of secondary bone grafting (SBG) on oral health-related and generic health-related quality of life (OHRQOL and HRQOL, respectively) in preadolescent orthodontic patients with alveolar bone defects. METHODS: We divided 101 orthodontic patients aged 8-10 years into 3 groups: 39 general orthodontic patients, 18 patients with orofacial clefts who did not require SBG, and 44 patients with alveolar defects who required SBG using particulate cancellous bone and marrow obtained from the iliac crest. The participants completed the self-report Child Perceptions Questionnaire (CPQ) and Paediatric Quality of Life Inventory (version 4.0) for OHRQOL and HRQOL, respectively, and their scores were assessed. The quality of life (QOL) of patients who required SBG was examined before, 1 month, and 6 months after SBG. The relationships between OHRQOL or HRQOL and potential patient factors were also evaluated. RESULTS: Physical HRQOL subscale scores worsened 1 month after SBG, whereas the total OHRQOL and HRQOL scores before and after SBG showed no significant changes. OHRQOL and HRQOL showed no significant differences among the 3 groups before SBG. The presence of oronasal fistula was associated with poorer OHRQOL in patients with cleft lip and/or palate. CONCLUSIONS: SBG and orthodontic treatment had a relatively small impact on the QOL of the preadolescent children in this study. Understanding the influence of SBG and patient factors on QOL would enable better treatment and care for these patients.

Oral administration of bovine lactoferrin suppresses the progression of rheumatoid arthritis in an SKG mouse model.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammatory bone destruction in which tumor necrosis factor alpha (TNF-α) plays a key role. Bovine lactoferrin (bLF) is a multifunctional protein with anti-inflammatory and immunomodulatory properties. This study aimed to clarify the inhibitory effects of bLF on the pathological progression of RA. The mannan-induced arthritis model in SKG mice (genetic RA model) was used. Orally applied liposomal bLF (LbLF) markedly reduced ankle joint swelling and bone destruction. Histologically, pannus formation and osteoclastic bone destruction were prevented in the LbLF-treated animals. Moreover, orally administered LbLF improved the balance between Th17 cells and regulatory T cells isolated from the spleen of mannan-treated SKG mice. In an in vitro study, the anti-inflammatory effects of bLF on TNF-α-induced TNF-α production and downstream signaling pathways were analyzed in human synovial fibroblasts from RA patients (RASFs). bLF suppressed TNF-α production from RASFs by inhibiting the nuclear factor kappa B and mitogen-activated protein kinase pathways. The intracellular accumulation of bLF in RASFs increased in an applied bLF dose-dependent manner. Knockdown of the lipoprotein receptor-related protein-1 (LRP1) siRNA gene reduced bLF expression in RASFs, indicating that exogenously applied bLF was mainly internalized through LRP-1. Immunoprecipitated proteins with anti-TNF receptor-associated factor 2 (TRAF2; an adapter protein/ubiquitin ligase) included bLF, indicating that bLF binds directly to the TRAF2-TRADD-RIP complex. This indicates that LbLF may effectively prevent the pathological progression of RA by suppressing TNF-α production by binding to the TRAF2-TRADD-RIP complex from the RASFs in the pannus. Therefore, supplemental administration of LbLF may have a beneficial effect on preventive/therapeutic reagents for RA.

An ex vivo organ culture screening model revealed that low temperature conditions prevent side effects of anticancer drugs.

Development of chemotherapy has led to a high survival rate of cancer patients; however, the severe side effects of anticancer drugs, including organ hypoplasia, persist. To assume the side effect of anticancer drugs, we established a new ex vivo screening model and described a method for suppressing side effects. Cyclophosphamide (CPA) is a commonly used anticancer drug and causes severe side effects in developing organs with intensive proliferation, including the teeth and hair. Using the organ culture model, we found that treatment with CPA disturbed the growth of tooth germs by inducing DNA damage, apoptosis and suppressing cellular proliferation and differentiation. Furthermore, low temperature suppressed CPA-mediated inhibition of organ development. Our ex vivo and in vitro analysis revealed that low temperature impeded Rb phosphorylation and caused cell cycle arrest at the G1 phase during CPA treatment. This can prevent the CPA-mediated cell damage of DNA replication caused by the cross-linking reaction of CPA. Our findings suggest that the side effects of anticancer drugs on organ development can be avoided by maintaining the internal environment under low temperature.

Effects of the carbonate content in carbonate apatite on bone replacement.

Carbonate apatite (CO3 Ap), an inorganic component of human bone, has been clinically applied as an artificial bone substitute. In this study, the effects of the CO3 content in CO3 Ap on the replacement by new bone were studied by fabricating CO3 Ap granules containing 0.9-8.3 wt% of CO3 . The dissolution rate of CO3 Ap in a weak acidic solution, mimicking the Howship's lacunae, was rapid for the CO3 Ap granules containing a larger amount of CO3 . Histological analyses demonstrated the rapid resorption in CO3 Ap and replacement by natural bone tissue when the CO3 content was increased. Therefore, the CO3 content in CO3 Ap is a key factor that influences the replacement of the bone tissue.

Stomatognathic functional improvement in a patient with a canted occlusal plane and temporomandibular disorder treated with an edgewise appliance and miniscrews.

Generally, a canted occlusal plane results in esthetic problems, such as an asymmetric mandible with midline deviation, and functional problems, such as temporomandibular disorder (TMD). For many years, orthognathic surgery has been used to level a canted occlusal plane. However, similar effects might be achieved by intruding the posterior teeth using a miniscrew. This case report describes a patient with a canted occlusal plane, mandibular deviation, shifted dental midlines, and TMD treated with an edgewise appliance using miniscrews as anchorage. Vertical control of posterior teeth with miniscrews enabled flattening of the canted occlusal plane. Dental midlines were coincided with the midfacial line, thereby improving smile symmetry. During 4 years of retention, the patient maintained ideal occlusion. Furthermore, TMD symptoms disappeared, and significant improvements in stomatognathic functions were observed compared with those at pretreatment. These results suggest that miniscrews can be used to improve canted occlusal plane and stomatognathic malfunctions.

Molecular imaging in masseter muscle observed by muscle function magnetic resonance imaging and 31 P-magnetic resonance spectroscopy in patients with a jaw deformity.

BACKGROUND: Skeletal mandibular protrusion would influence to the muscle fatigue of the masticatory muscles. Establishing a diagnostic procedures combining physiological and biochemical information is necessary for quantitative evaluation of masticatory muscle fatigue. OBJECTIVE: The transverse relaxation time (T2 time) of muscle functional magnetic resonance imaging (mfMRI), and 31 P-magnetic resonance spectroscopy (MRS) were used to investigate the reliability as parameters for measuring the masseter muscle in patients with skeletal mandibular prognathism. METHOD: The subjects were 19 patients diagnosed as skeletal mandibular protrusions and 19 healthy subjects as a control group. Transverse relaxation time (T2 value) determined by mfMRI along with creatine phosphate (PCr) and inorganic phosphorus (Pi) determined by 31 P-MRS before, during, and after clenching were used for molecular imaging of muscle fatigue. RESULTS: The average T2 value of the patient group was significantly higher than that of the healthy control group at rest. Furthermore, the average T2 value transiently increased in both groups during experimental clenching. The PCr and Pi showed a tendency toward a transient decrease and increases, respectively. The pH in the masseter muscle showed a transient decrease in both groups prior to and following experimental clenching. The pH in the masseter muscle of the patient group was significantly lower than that in the healthy control group at rest and recovery. CONCLUSION: We showed mfMRI and 31 P-MRS are useful for evaluating masseter fatigue during clenching, and the masseter muscle in the prognathic patients showed more severe fatigue than the healthy controls.

Deletion of epithelial cell-specific p130Cas impairs the maturation stage of amelogenesis.

Amelogenesis consists of secretory, transition, maturation, and post-maturation stages, and the morphological changes of ameloblasts at each stage are closely related to their function. p130 Crk-associated substrate (Cas) is a scaffold protein that modulates essential cellular processes, including cell adhesion, cytoskeletal changes, and polarization. The expression of p130Cas was observed from the secretory stage to the maturation stage in ameloblasts. Epithelial cell-specific p130Cas-deficient (p130CasΔepi-) mice exhibited enamel hypomineralization with chalk-like white mandibular incisors in young mice and attrition in aged mouse molars. A micro-computed tomography analysis and Vickers micro-hardness testing showed thinner enamel, lower enamel mineral density and hardness in p130CasΔepi- mice in comparison to p130Casflox/flox mice. Scanning electron microscopy, and an energy dispersive X-ray spectroscopy analysis indicated the disturbance of the enamel rod structure and lower Ca and P contents in p130CasΔepi- mice, respectively. The disorganized arrangement of ameloblasts, especially in the maturation stage, was observed in p130CasΔepi- mice. Furthermore, expression levels of enamel matrix proteins, such as amelogenin and ameloblastin in the secretory stage, and functional markers, such as alkaline phosphatase and iron accumulation, and Na+/Ca2++K+-exchanger in the maturation stage were reduced in p130CasΔepi- mice. These findings suggest that p130Cas plays important roles in amelogenesis (197 words).

Three-Dimensional Geometric Morphometry of Facial Soft Tissue Changes After Bilateral Sagittal Split Ramus Osteotomy.

ABSTRACT: This study aimed to evaluate the performance of geometric morphometry (GM) to assess the changes in facial soft tissue after orthognathic surgery. Subjects were 27 patients (skeletal class III) who underwent bilateral sagittal split ramus osteotomy and 27 volunteers as a control group. Computed tomography images of each patient were obtained before surgery (T0) and 6 months after surgery (T1). Computed tomography images of 27 volunteers (skeletal class I) were also obtained as a control group. Using a three-dimensional (3D) modeling software, 3D models were created and exported to a 3D surface analyzing software for geometric morphometry and principal component (PC) analysis. Significant differences in facial soft tissue were found in the first and second of 15 PC. The first PC represented variation in the lower facial height, and the second PC represented variation in the anterior-posterior position of the chin. Comparing the pre- and post-operative images, they illustrated that lower facial height was decreased, and the chin and lower lip moved posteriorly. Geometric morphometry showed to be a successful tool to isolate surgery-related changes from interindividual morphological variations.

Modulation of osteoclastogenesis through adrenomedullin receptors on osteoclast precursors: initiation of differentiation by asymmetric cell division.

Adrenomedullin (ADM), a member of the calcitonin family of peptides, is a potent vasodilator and was shown to have the ability to modulate bone metabolism. We have previously found a unique cell surface antigen (Kat1 antigen) expressed in rat osteoclasts, which is involved in the functional regulation of the calcitonin receptor (CTR). Cross-linking of cell surface Kat1 antigen with anti-Kat1 antigen monoclonal antibody (mAbKat1) stimulated osteoclast formation only under conditions suppressed by calcitonin. Here, we found that ADM provoked a significant stimulation in osteoclastogenesis only in the presence of calcitonin; a similar biological effect was seen with mAbKat1 in the bone marrow culture system. This stimulatory effect on osteoclastogenesis mediated by ADM was abolished by the addition of mAbKat1. 125I-labeled rat ADM (125I-ADM)-binding experiments involving micro-autoradiographic studies demonstrated that mononuclear precursors of osteoclasts abundantly expressed ADM receptors, and the specific binding of 125I-ADM was markedly inhibited by the addition of mAbKat1, suggesting a close relationship between the Kat1 antigen and the functional ADM receptors expressed on cells in the osteoclast lineage. ADM receptors were also detected in the osteoclast progenitor cells in the late mitotic phase, in which only one daughter cell of the dividing cell express ADM receptors, suggesting the semiconservative cell division of the osteoclast progenitors in the initiation of osteoclastogenesis. Messenger RNAs for the receptor activity-modifying-protein 1 (RAMP1) and calcitonin receptor-like receptor (CRLR) were expressed in cells in the osteoclast lineage; however, the expression of RAMP2 or RAMP3 was not detected in these cells. It is suggested that the Kat1 antigen is involved in the functional ADM receptor distinct from the general ADM receptor, consisting of CRLR and RAMP2 or RAMP3. Modulation of osteoclastogenesis through functional ADM receptors abundantly expressed on mononuclear osteoclast precursors is supposed to be important in the fine regulation of osteoclast differentiation in a specific osteotrophic hormonal condition with a high level of calcitonin in blood.

Characteristics of craniofacial morphology and factors affecting them in patients with isolated cleft palate.

BACKGROUND: Myriad maxillo-mandibular occlusal relationships are observed in patients with isolated cleft palate (ICP), unlike in patients with other cleft types, such as cleft lip and palate. OBJECTIVES: This study aimed to categorise the characteristics of craniofacial morphology in patients with ICP, and investigate the clinical factors affecting these categorised morphological characteristics. METHODS: Thirty-six girls with ICP (age (mean ± SD): 5.36 ± 0.36 years) underwent cephalometric measurement. Their craniofacial morphology was categorised using cluster analysis. Profilograms were created and superimposed onto the standard Japanese profilograms to visualise the morphological characteristics of each group (cluster). The mean values and variations in the linear and angular measurements of each group were compared with the Japanese standards and statistically analysed using Dunnett's test after the analysis of variance. Fisher's exact test was used to analyse the differences between the cleft types (cleft in the hard and/or soft palate) and skills of the operating surgeons in the groups. RESULTS: Cluster analysis of craniofacial morphologies in patients with ICP resulted in the formation of three categories: the first cluster exhibited a relatively harmonious anteroposterior relationship between the maxilla and the mandible (22.2%); the second cluster exhibited crossbite owing to a significantly smaller maxilla (33.3%); and the third cluster exhibited a smaller mandible with posterior rotation showing skeletal class II malocclusion (44.4%). Differences in cleft types and surgeons were not associated with the distribution of patients in each cluster. CONCLUSIONS: Patients with ICP exhibited characteristic morphological patterns, such as bimaxillary retrusion or severe mandibular retrusion, besides the anterior crossbite frequently found in patients with cleft lip and palate . Understanding the typical morphological characteristics could enable better diagnostic categorisation of patients with ICP, which may eventually improve orthodontic treatment planning.

Mathematical modeling of palatal suture pattern formation: morphological differences between sagittal and palatal sutures.

The median palatal suture serves as a growth center for the maxilla; inadequate growth at this site causes malocclusion and dental crowding. However, the pattern formation mechanism of palatal sutures is poorly understood compared with that of calvarial sutures such as the sagittal suture. In the present study, therefore, we compared the morphological characteristics of sagittal and palatal sutures in human bone specimens. We found that palatal suture width was narrower than sagittal suture width, and the interdigitation amplitude of the palatal suture was lower than that of the sagittal suture. These tendencies were also observed in the neonatal stage. However, such differences were not observed in other animals such as chimpanzees and mice. We also used a mathematical model to reproduce the differences between palatal and sagittal sutures. After an extensive parameter search, we found two conditions that could generate the difference in interdigitation amplitude and suture width: bone differentiation threshold [Formula: see text] and growth speed c. We discuss possible biological interpretations of the observed pattern difference and its cause.

Systemic Exposure to Lipopolysaccharide from Porphyromonas gingivalis Induces Bone Loss-Correlated Alzheimer's Disease-Like Pathologies in Middle-Aged Mice.

BACKGROUND: Alzheimer's disease (AD) and bone loss are clinically exacerbated. However, the mechanism of exacerbation remains understood. OBJECTIVE: We tested our hypothesis that periodontitis is involved in the exacerbation, contributing to AD pathologies. METHODS: The bone, memory, and inflammation in bone and brain were examined in 12-month-old mice after systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (P gLPS) for 3 consecutive weeks. RESULTS: Compared with control mice, bone loss in tibia (26% decrease) and memory decline (47% decrease) were induced in mice with a positive correlation after exposure to P gLPS (r = 0.7378, p = 0.0011). The IL-6 and IL-17 expression in tibia was negatively correlated with the bone volume/total tissue volume (r = -0.6619, p = 0.0052; r = -0.7129, p = 0.0019), while that in the cortex was negatively correlated with the memory test latency (r = -0.7198, p = 0.0017; p = 0.0351, r = -0.5291). Furthermore, the IL-17 expression in microglia was positively correlated with Aß42 accumulation in neurons (r = 0.8635, p < 0.0001). In cultured MG6 microglia, the P gLPS-increased IL-6 expression was inhibited by a PI3K-specific inhibitor (68% decrease), and that of IL-17 was inhibited by IL-6 antibody (41% decrease). In cultured N2a neurons, conditioned medium from P gLPS-stimulated microglia (MCM) but not P gLPS increased the productions of AßPP, CatB, and Aß42, which were significantly inhibited by pre-treatment with IL-17 antibody (67%, 51%, and 41% decrease). CONCLUSION: These findings demonstrated that chronic systemic exposure to P gLPS simultaneously induces inflammation-dependent bone loss and AD-like pathologies by elevating IL-6 and IL-17 from middle age, suggesting that periodontal bacteria induce exacerbation of bone loss and memory decline, resulting in AD progression.

The development, validation, and psychometric properties of the Japanese version of the Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) for school-age children.

BACKGROUND: This study was performed to develop and validate a Japanese version of Child Oral Health Impact Profile-Short Form (COHIP-SF) 19 and to assess its psychometric properties in Japanese school-age children. METHODS: The original English COHIP-SF 19 was translated into Japanese (COHIP-SF 19 JP) using a standard forward and backward translation procedure. The psychometric properties of the COHIP-SF 19 JP were assessed in 379 public school students between 7 and 18 years of age in Fukuoka, Japan. Internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation coefficient, ICC) were the metrics used for evaluation of this questionnaire. The discriminant validly was examined using the Wilcoxon rank sum test to identify significant differences in COHIP-SF 19 JP scores according to the results of dental examinations. The convergent validity was examined using the Spearman correlations to determine the relationships between COHIP-SF 19 JP scores and the self-perceived oral health ratings. Confirmatory factor analyses (CFA) were performed to verify the factor structure of the questionnaire. RESULTS: The COHIP-SF 19 JP revealed good internal consistency (Cronbach's alpha, 0.77) and test-retest reliability (ICC, 0.81). Discriminant validity indicated that children with dental caries or malocclusion had significantly lower COHIP-SF 19 JP scores (P <  0.05); convergent validity indicated that the self-perceived oral health rating was significantly correlated with the COHIP-SF 19 JP total score and subscores (rs = 0.352-0.567, P <  0.0001), indicating that the questionnaire had a sufficient construct validity. CFA suggested that the modified four-factor model had better model fit indices than the original three-factor model. CONCLUSION: The collected data showed that the COHIP-SF 19 JP possesses sufficient psychometric properties for use in Japanese school-age children.