Facilitation of Bone Healing Processes Based on the Developmental Function of Meox2 in Tooth Loss Lesion.

In the present study, we examined the bone healing capacity of Meox2, a homeobox gene that plays essential roles in the differentiation of a range of developing tissues, and identified its putative function in palatogenesis. We applied the knocking down of Meox2 in human periodontal ligament fibroblasts to examine the osteogenic potential of Meox2. Additionally, we applied in vivo periodontitis induced experiment to reveal the possible application of Meox2 knockdown for 1 and 2 weeks in bone healing processes. We examined the detailed histomorphological changes using Masson's trichrome staining and micro-computed tomography evaluation. Moreover, we observed the localization patterns of various signaling molecules, including α-SMA, CK14, IL-1ß, and MPO to examine the altered bone healing processes. Furthermore, we investigated the process of bone formation using immunohistochemistry of Osteocalcin and Runx2. On the basis of the results, we suggest that the knocking down of Meox2 via the activation of osteoblast and modulation of inflammation would be a plausible answer for bone regeneration as a gene therapy. Additionally, we propose that the purpose-dependent selection and application of developmental regulation genes are important for the functional regeneration of specific tissues and organs, where the pathological condition of tooth loss lesion would be.

Age-Associated Tooth Loss and Oral Microbial Dysbiosis in a Mouse Genetic Model of Chronic Nicotine Exposure.

Nicotine acts as a potent modulator of normal cellular responses through the nicotinic acetylcholine receptor subtype alpha7. In a mouse genetic model of alpha7 receptor dysfunction, alpha7E260A:G, 85 percent of 18 month-old mice exhibit an age-associated spontaneous loosening or complete loss of 3rd molars that was not present in the control mice. The adjacent soft tissues appeared largely unaffected. Further analysis including micro-CT revealed evidence of bone loss surrounding the 3rd molars with areas of cavitation and/or sponge-like (cancellous) bone remodeling in the mandible. The mandible microbiome was examined using 16S-rRNA sequencing. The results show the alpha7E260A:G oral microbiome included increased landscape complexity indicative of dysbiosis, and a significant increase of some bacteria, particularly Staphylococcus. These results suggest that normal alpha7 function plays a relevant role in maintaining normal gene expression and oral microbiome stasis. Consequently, this mouse model suggests there are consequences to ongoing alpha7 receptor dysfunction and oral health, as can occur from chronic exposure to nicotine as expected from electronic nicotine delivery systems (ENDS or "vaping"), that may not be seen until older age.

Neurodegeneration of Trigeminal Mesencephalic Neurons by the Tooth Loss Triggers the Progression of Alzheimer's Disease in 3×Tg-AD Model Mice.

BACKGROUND: The mesencephalic trigeminal nucleus (Vmes) is not only anatomically adjacent to the locus coeruleus (LC) but is also tightly associated with the function of the LC. The LC can be the first area in which Alzheimer's disease (AD) develops, although it is unclear how LC neuronal loss occurs. OBJECTIVE: We investigated whether neuronal death in the Vmes can be spread to adjacent LC in female triple transgenic (3×Tg)-AD mice, how amyloid-ß (Aß) is involved in LC neuronal loss, and how this neurodegeneration affects cognitive function. METHODS: The molars of 3×Tg-AD mice were extracted, and the mice were reared for one week to 4 months. Immunohistochemical analysis, and spatial learning/memory assessment using the Barnes maze were carried out. RESULTS: In 4-month-old 3×Tg-AD mice, aggregated cytotoxic Aß42 was found in granules in Vmes neurons. Neuronal death in the Vmes occurred after tooth extraction, resulting in the release of cytotoxic Aß42 and an increase in CD86 immunoreactive microglia. Released Aß42 damaged the LC, in turn inducing a significant reduction in hippocampal neurons in the CA1 and CA3 regions receiving projections from the LC. Based on spatial learning/memory assessment, after the tooth extraction in the 4-month-old 3×Tg-AD mice, increased latency was observed in 5-month-old 3×Tg-AD mice 1 month after tooth extraction, which is similar increase of latency observed in control 8-month-old 3×Tg-AD mice. Measures of cognitive deficits suggested an earlier shift to dementia-like behavior after tooth extraction. CONCLUSION: These findings suggest that tooth extraction in the predementia stage can trigger the spread of neurodegeneration from the Vmes, LC, and hippocampus and accelerate the onset of dementia.

The Association of Periodontitis and Peripheral Arterial Occlusive Disease-A Systematic Review.

Background: Observational studies support an association between periodontitis (PD) and atherosclerotic vascular disease, but little is known specifically about peripheral arterial occlusive disease (PAOD). OBJECTIVES: To systematically review the evidence for an association between PD and PAOD. DATA SOURCES: Medline via PubMed. REVIEW METHODS: We searched the Pubmed database for original studies, case reports, case series, meta-analyses and systematic reviews that assessed whether there is an association between PD (all degrees of severity) and PAOD (all degrees of severity). The reporting of this systematic review was in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement following the Population, Intervention, Control, and Outcome (PICO) format. RESULTS: 17 out of 755 detected studies were included in the qualitative synthesis. Nine studies demonstrated associations between PD and PAOD, and two studies reported associations between tooth loss and PAOD. Six studies addressed the pathomechanism regarding PD as a possible trigger for PAOD. No study that dismissed an association could be detected. Odds ratios or hazard ratios ranged from 1.3 to 3.9 in four large cohort studies after adjusting for established cardiovascular risk factors. CONCLUSIONS: The presented evidence supports a link between PD and PAOD. Further studies which address the temporality of PD and PAOD and randomized controlled intervention trials examining the causal impact of PD on PAOD are needed. Although our results cannot confirm a causal role of PD in the development of PAOD, it is likely that PD is associated with PAOD and plays a contributing role.

Relationship between salivary haemoglobin and number of remaining teeth in older Koreans.

OBJECTIVE: We investigated the relationship between saliva and dental biofilm characteristics, oral hygiene behaviours and the number of remaining teeth in a sample of older Koreans. MATERIALS AND METHODS: This cross-sectional study included 133 participants, aged 65 years and older, recruited from senior welfare facilities in Incheon, South Korea. The outcome variable was the number of remaining teeth, and its associations with the independent variables of participants' general characteristics, salivary haemoglobin level, dental biofilm acidogenicity, salivary flow rate and oral hygiene behaviours were assessed. For statistical analyses, chi-squared test and step-wise multiple linear regression were used. RESULTS: The multiple linear regression model, which included all related factors identified in the bivariate analyses, showed that older adults who had high salivary haemoglobin levels (P < .05), brushed their teeth using the horizontal scrub method (P< .001), and did not use an interproximal cleaning device (P < .01) were more likely to have fewer remaining teeth. However, dental biofilm acidogenicity was not associated with the number of remaining teeth. CONCLUSION: The number of remaining teeth was associated with salivary haemoglobin level, appropriate toothbrushing technique and interdental cleaning. These findings suggest that the monitoring of salivary haemoglobin may contribute to the prevention of tooth loss caused by periodontal disease.

Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice.

BACKGROUND: It is known that tooth loss is known to be a risk factor for Alzheimer's disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer's disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNF-related mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). RESULTS: At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. CONCLUSIONS: These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does.

Whole salivary interleukin-6 and matrix metalloproteinase-8 levels in patients with chronic periodontitis with and without prediabetes.

BACKGROUND: The cytokine profile in unstimulated whole saliva (UWS) of patients with prediabetes and chronic periodontitis (CP) remains uninvestigated. The aim of this study is to assess interleukin (IL)-6 and matrix metalloproteinase (MMP)-8 levels in UWS of patients with CP with and without prediabetes. METHODS: Eighty-eight males (aged 39 to 51 years) were divided into three groups: group 1: 28 patients with CP and prediabetes; group 2: 30 patients with CP and without prediabetes; and group 3: 30 controls. Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels, periodontal parameters (plaque index, bleeding on probing, probing depth, attachment loss, and marginal bone loss), and number of missing teeth were recorded. UWS samples were collected, and UWS flow rate (UWSFR) was measured. IL-6 and MMP-8 were measured in UWS using enzyme-linked immunosorbent assay. P values <0.05 were considered statistically significant. RESULTS: Mean FBG and HbA1c levels were significantly higher in group 1 (119.3 ± 3.1 mg/dL and 6.1% ± 0.2%) than group 2 (80.1 ± 3.5 mg/dL and 4.8% ± 0.5%; P <0.001) and group 3 (75.3 ± 2.2 mg/dL and 4.3% ± 0.2%; P <0.05). UWSFR was significantly higher in groups 2 (0.53 ± 0.1 mL/minute; P <0.05) and 3 (0.51 ± 0.1 mL/minute; P <0.01) than group 1 (0.33 ± 0.05 mL/minute). Periodontal parameters were worse in group 1 (P <0.05) and group 2 (P <0.05) than group 3. There was no difference in periodontal parameters, numbers of missing teeth, or salivary IL-6 and MMP-8 levels between patients in groups 1 and 2. CONCLUSION: Salivary IL-6 and MMP-8 levels are elevated in patients with CP with and without prediabetes.

The effect of posterior tooth loss on the expression of type II collagen, IL-1ß and VEGF in the condylar cartilage of growing rats.

OBJECTIVE: The aim of this study was to evaluate the effect of unilateral and bilateral loss of posterior occlusal support on the expression of type II collagen, interleukin-1ß and VEGF in the condylar cartilage of growing rats. DESIGN: Thirty female Wistar rats (5 weeks old) were randomized into three groups: control, unilateral extraction of mandibular molar teeth, bilateral extraction of mandibular molar teeth. Animals were sacrificed 8 weeks after tooth extraction and the temporomandibular joints were prepared for immunohistochemical analysis. RESULTS: Bilateral molar extraction increased the expression of interleukin-1ß (P<0.01) and VEGF (P<0.01), while unilateral extraction increased the expression of interleukin-1ß (P<0.05) and type II collagen (P<0.01). The expression of VEGF was higher on the extracted than on the non-extracted side (P<0.01) after unilateral extraction. CONCLUSION: Loss of posterior occlusal support alters the expression of type II collagen, interleukin-1ß and VEGF in the condylar cartilage of rats. The expression pattern of these proteins is different when loss of occlusal support was bilateral or unilateral, including differences between extracted and non-extracted sides.

Influence of unilateral tooth loss in the temporomandibular joint and masseter muscle of rabbits.

OBJECTIVE: The purpose of this study was to evaluate the influence of the masticatory system in patients with missing teeth. STUDY DESIGN: The influence of tooth loss on the masticatory system was analyzed with the use of bone scintigraphy ((99m)Tc-MDP) and histochemistry. Eight white rabbits (New Zealand, 12 weeks old) were used. The rabbits were divided into 2 groups: 6 weeks and 12 weeks. Teeth were extracted unilaterally in each rabbit under general anesthesia. Six and 12 weeks after extraction, scintigraphy was conducted, and the rabbits were killed and their masseter muscles removed for histochemical analysis. RESULTS: The results of bone metabolism (relative ratio) measured by bone scintigraphy were 48.27% at extraction sites and 51.73% at nonextraction sites at 6 weeks and 39.96% at extraction sites and 60.04% at nonextraction sites at 12 weeks. There was a significant difference at 12 weeks (P < .05). Tissue calcium contents and osteoclast counts showed different results between the extraction and nonextraction sites, but these differences did not reach statistical significance. CONCLUSIONS: The bone metabolism of temporomandibular joints and histochemical aspects of masticatory muscles may be associated with occlusal alterations following tooth loss.

Relationship between radiographic changes in the temporomandibular joint and bone mineral density: a population based study.

OBJECTIVE. The aim of this population based study was to compare radiographic changes in the temporomandibular joint (TMJ) with the lumbar spine and femoral neck BMD. To find whether there is any relationship between TMJ radiographic changes, vitamin D (25(OH)D) and bone markers levels and the number of missing teeth. MATERIAL AND METHODS. The study included 95 randomly selected participants. Bilateral TMJ images were obtained using an orthopantomograph (OPTG) and were evaluated for presence of radiographic signs. BMD was measured by dual energy X-ray absorptiometry (DXA). BMD of the lumbar spine (LT score) and femur (FT score) was detected by DXA. The level of type I collagen telopeptide fragments (P1NP), of C-telopeptide crosslaps of type I collagen (CTX-1) and of 25(OH)D were also measured. RESULTS. Subjects with a lower LT score had significantly fewer occluding pairs of teeth (p=0.018) and were more frequent users of removable prostheses (p=0.008). Radiographic changes were negatively correlated with P1NP (p=0.041). CTX-1 correlated positively with P1NP (p<0.001) and negatively with 25(OH)D (p=0.042). Occluding pairs of teeth were positively correlated with the LT score (p=0.012) and FT score (p<0.001). Radiography showed changes in the TMJ of 57% of participants. Out of 95 participants, 60% demonstrated an abnormally low LT value. CONCLUSIONS. This population based study indicates that TMJ radiographic changes and teeth loss seems to be related to the low level of BMD and 25(OH)D level.

Cumulative lead exposure and tooth loss in men: the normative aging study.

BACKGROUND: Individuals previously exposed to lead remain at risk because of endogenous release of lead stored in their skeletal compartments. However, it is not known if long-term cumulative lead exposure is a risk factor for tooth loss. OBJECTIVES: We examined the association of bone lead concentrations with loss of natural teeth. METHODS: We examined 333 men enrolled in the Veterans Affairs Normative Aging Study. We used a validated K-shell X-ray fluorescence (KXRF) method to measure lead concentrations in the tibial midshaft and patella. A dentist recorded the number of teeth remaining, and tooth loss was categorized as 0, 1-8 or > or = 9 missing teeth. We used proportional odds models to estimate the association of bone lead biomarkers with tooth loss, adjusting for age, smoking, diabetes, and other putative confounders. RESULTS: Participants with > or = 9 missing teeth had significantly higher bone lead concentrations than those who had not experienced tooth loss. In multivariable-adjusted analyses, men in the highest tertile of tibia lead (> 23 microg/g) and patella lead (> 36 microg/g) had approximately three times the odds of having experienced an elevated degree of tooth loss (> or = 9 vs. 0-8 missing teeth or > or = 1 vs. 0 missing teeth) as those in the lowest tertile [prevalence odds ratio (OR) = 3.03; 95% confidence interval (CI), 1.60-5.76 and OR = 2.41; 95% CI, 1.30-4.49, respectively]. Associations between bone lead biomarkers and tooth loss were similar in magnitude to the increased odds observed in participants who were current smokers. CONCLUSION: Long-term cumulative lead exposure is associated with increased odds of tooth loss.

Number of teeth and serum lipid peroxide in 85-year-olds.

OBJECTIVES: To investigate influence of dental status on systemic oxidative stress, we evaluated the association between number of teeth and serum lipid peroxide, an oxidative stress index, in 85-years old residents of Japan. METHODS: In October 2003, 207 subjects 85-years old agreed to participate in the present follow-up study after five years from the 8020 Data Bank Survey of Fukuoka prefecture in 1998. Dental health condition including number of teeth was examined by dentists. Data from 204 subjects (88 male, 116 female) who completed nonfasting venous blood examination including lipid peroxide and blood chemistry were analyzed. The examination included a medical questionnaire regarding smoking history, physical activity, alcohol consumption, educational duration, and regular dental care, anthropometric and manometric measurements. RESULTS: Albumin, lipids, and lipid peroxide in serum all were within the normal range. Number of teeth correlated positively with height and white blood cell count, and correlated negatively with lipid peroxide. In a multiple regression analysis to adjust for confounding factors, tooth number retained this correlation with lipid peroxide. By analysis of variance with a Bonferroni-Dunn correction, edentulous subjects showed significantly higher lipid peroxide than those retaining 20 teeth or more. CONCLUSION: The negative association between number of teeth and lipid peroxide links more teeth remaining with less oxidative stress in an 85-year-old population; this may decrease risk of atherosclerotic complications.

[The biochemical changes of hippocampus in patients before and after denture restoration: a preliminary 1H-magnetic resonance spectroscopy study].

OBJECTIVE: To study the effects of reconstruction of lost occlusal support on the biochemical changes of nervous system. METHODS: The changes of central nervous system metabolic compounds within hippocampus body were measured with proton magnetic resonance spectroscopy ((1)HMRS) before and after denture restoration (six weeks) in seven patients with prolonged loss of occlusal support. RESULTS: (1)HMRS indicated that Cho/Cr decreased by 11.9% (P < 0.05) six weeks after denture restoration, MI/Cr decreased by 28.8% (P < 0.05), and NAA/CR increased by 4.8% (P > 0.05) within hippocampus body. CONCLUSIONS: Recovery of occlusal support facilitates improvement of neuron functions in patients' hippocampus, which may help improve the functions of nervous system.

Bone loss and teeth.

Loss of teeth results in irreversible alveolar bone resorption, and untreated dental disease causes alveolar bone lysis that ultimately leads to loss of teeth. In addition to anchoring the teeth in the alveolar ridge, the maxillary and mandibular bone allows dental restoration procedures, such as construction of root-supported implants, fixed dentures, or removable dentures. However, the functional and cosmetic results depend on the quantity and quality of the maxillary or mandibular bone, which can be affected by many normal and abnormal processes. The alveoli are particularly fragile and labile. Changes in alveolar bone vary considerably across individuals and depend directly on local factors. Many studies have investigated associations between alveolar bone status and bone mass at other skeletal sites. These studies focused chiefly on the course of parodontal disease, alveolar ridge resorption after tooth extraction, and density differences across various mandibular sites. They produced conflicting results, probably because of differences in measurement methods. Measurement sites and methods should be standardized to ensure that reliable and comparable data are obtained. To date, there are few reliable methods for obtaining quantitative measurements of bone mineral content in maxillary and mandibular bone.

Influence of tooth-loss and concomitant masticatory alterations on cholinergic neurons in rats: immunohistochemical and biochemical studies.

The influence of tooth loss on the viability of cholinergic neurons was examined in rats. At 25th postnatal week, rats were divided into the three groups; a control group fed a solid diet, a soft diet group fed a powder diet and a molar crown-less group in which all molar crowns were removed and the powder diet was given. At 15 and 35 weeks post-treatment, the number of choline acetyltransferase (ChAT)-positive neurons in the nucleus of the diagonal band/medial septal nucleus (NDB/MS) was significantly smaller in the molar crown-less group than in the control group (P < 0.01). This was not the case in the pedunculopontine tegmental nucleus or (PPT) or in the trigeminal motor nucleus. Biochemical assay showed no statistically significant differences in choline concentrations in the hippocampus between the control and the molar crown-less group both at 15 and at 35 weeks post-treatment. Nevertheless, acetylcholine (ACh) concentration in the hippocampus of the molar crown-less group was significantly lower than that of the control group at 15 weeks post-treatment (P < 0.05). Taken together, a decrease of oral sensory information may have caused a reduction in the number of ChAT-positive neurons selectively in NDB/MS, which in turn caused a decline of ACh concentrations in the hippocampus.

Calcium and other salivary factors in periodontitis-affected subjects prior to treatment.

Salivary calcium was shown to be higher in treated periodontitis-affected subjects (P+) than in periodontitis-free patients (P-). Here the aim was to study whether differences in calcium or other salivary factors exist prior to treatment. The test group consisted of 20 (15 men, 5 women) periodontitis-affected subjects and the control group 15 subjects (10 men, 5 women) free from periodontitis. Paraffin-stimulated whole saliva was collected to determine the flow-rate, calcium and phosphate concentrations, pH, buffering capacity, numbers of mutans streptococci, lactobacilli and yeasts. The results showed a higher calcium concentration (p < 0.05) in the P+ group (mean: 1.68 mmol/l; SE: 0.06 in men and mean: 1.49 mmol/l; SE: 0.10 in women) than in the P-group (mean: 1.48 mmol/l; SE: 0.09 in men and mean: 1.18 mmol/l; SE: 0.10 in women). The P+ group had more intact teeth (mean +/- SE: 9.9 +/- 0.8 in men and 11.2 +/- 2.0 in women) than the P-group (mean +/- SE: 8.3 +/- 0.7 in men and 8.2 +/- 2.4 in women). The present findings may indicate that an elevated level of salivary Ca is characteristic of P+ patients both before and after periodontal treatment.