Self-reported oral health is associated with systemic health outcomes and all-cause mortality.

BACKGROUND: Self-reported oral health questions (OHQs) are used commonly for epidemiologic surveillance of periodontal disease (PD). The authors' objective was to investigate how OHQs are associated with well-established systemic comorbidities of PD and their impact on all-cause mortality. The authors hypothesized that OHQs exhibit associations with systemic comorbidities similar to PD. METHODS: Two independent data sets were used to achieve these objectives: the Women's Health Study, a prospective cohort of women 45 years or older with self-reported information on PD, OHQs, cardiovascular disease, diabetes, and osteoporosis in various timeframes (continuous from 1992) and the National Health and Nutrition Examination Survey (NHANES), with data on OHQs and linked mortality (1999-2018). The authors applied multivariate logistic regression models and Cox proportional hazard regression survival analyses to test their hypotheses. RESULTS: The Women's Health Study participants who reported having PD until 2006 were more likely to later report deteriorating oral health, bone loss around their teeth, or periodontal treatment in 2018. Self-rated fair or poor oral health was independently associated with increased risk of cardiovascular disease (odds ratio, 1.39; 95% CI, 1.14 to 1.69; P < .001), diabetes (odds ratio, 1.21; 95% CI, 1.02 to 1.43; P = .028), and osteoporosis (odds ratio, 1.60; 95% CI, 1.38 to 1.84; P < .001). National Health and Nutrition Examination Survey participants who self-rated fair or poor oral health had higher risks of all-cause mortality (hazard ratio, 1.18; 95% CI, 1.02 to 1.37; P = .027). CONCLUSIONS: Self-reported oral health had a similar magnitude of associations with systemic comorbidities as established with PD previously. Moreover, self-rated fair or poor oral health, suboptimal dental visits, or infrequent flossing were associated with increased all-cause mortality. PRACTICAL IMPLICATIONS: These results support the use of OHQs in assessing systemic connections, especially when clinical dental access is limited. This clinical trial was registered at ClinicalTrials.gov. The registration number is NCT00000479.

An In Vitro Pilot Study on the Effects of Silver Diamine Fluoride on Periodontal Pathogens and Three-Dimensional Scaffolds of Human Fibroblasts and Epithelial Cells.

Objective: The aims of this study were to investigate the antibacterial and cytotoxic effects of silver diamine fluoride (SDF) on periodontal pathogens and human skin constructs, respectively. Background: SDF has been proven to have bactericidal effects on cariogenic bacteria. No studies to date evaluated the bactericidal effects of SDF on periodontal pathogens nor its effect on epithelium and fibroblasts. Methods: Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans were cultured in monospecies biofilms, exposed to increasing concentrations of SDF and inoculated on agar plates to assess viability. Human gingival fibroblasts in 2D cultures were exposed to 1 µL of 0.394% of SDF and viewed using real-time imaging. Finally, SDF was applied to human, 3D tissue scaffolds of fibroblasts and keratinocytes, and termed human skin equivalents (HSE). A clinical dose of 38% SDF was applied, and HSE were cultured for 12 hours, 1, 3, 5, and 10 days. The tissue was observed clinically and histologically with hematoxylin and eosin staining and TUNEL. Results: S. mutans and A. actinomycetemcomitans growth was completely inhibited using all dilutions of SDF, whereas P. gingivalis was still viable with 0.197% and 0.098% of SDF. Single-layer fibroblasts experienced immediate necrosis upon contact with SDF. Application of SDF to HSE showed maturation of a whitish lesion within 24 hours, followed by pigmented, crusted tissue after 3 days. Histological evaluation of treated tissues showed apoptotic cells in the epithelium and upper half of the connective tissue. Conclusion: Our data suggest that SDF has bactericidal properties against two periodontal pathogens: P. gingivalis and A. actinomycetemcomitans. SDF caused immediate necrosis of monolayer fibroblasts, but does not extend to the full extent of layered fibroblasts in HSE.

Candidate loci shared among periodontal disease, diabetes and bone density.

Introduction: While periodontal disease (PD) has been associated with type 2 diabetes (T2D) and osteoporosis, the underlying genetic mechanisms for these associations remain largely unknown. The aim of this study is to apply cross-trait genetic analyses to investigate the potentially shared biology among PD, T2D, and bone mineral density (BMD) by assessing pairwise genetic correlations and searching for shared polymorphisms. Methods: We applied cross-trait genetic analyses leveraging genome-wide association study (GWAS) summary statistics for: Periodontitis/loose teeth from the UKBB/GLIDE consortium (PerioLT, N=506594), T2D from the DIAGRAM consortium (Neff=228825), and BMD from the GEFOS consortium (N=426824). Among all three, pair-wise genetic correlations were estimated with linkage disequilibrium (LD) score regression. Multi-trait meta-analysis of GWAS (MTAG) and colocalization analyses were performed to discover shared genome-wide significant variants (pMTAG <5x10-8). For replication, we conducted independent genetic analyses in the Women's Genome Health Study (WGHS), a prospective cohort study of middle-aged women of whom 14711 provided self-reported periodontal disease diagnosis, oral health measures, and periodontal risk factor data including incident T2D. Results: Significant genetic correlations were identified between PerioLT/T2D (Rg=0.23; SE=0.04; p=7.4e-09) and T2D/BMD (Rg=0.09; SE=0.02; p=9.8e-06). Twenty-one independent pleiotropic variants were identified via MTAG (pMTAG<5x10-8 across all traits). Of these variants, genetic signals for PerioLT and T2D colocalized at one candidate variant (rs17522122; ProbH4 = 0.58), a 3'UTR variant of AKAP6. Colocalization between T2D/BMD and the original PerioLT GWAS p-values suggested 14 additional loci. In the independent WGHS sample, which includes responses to a validated oral health questionnaire for PD surveillance, the primary shared candidate (rs17522122) was associated with less frequent dental flossing [OR(95%CI)= 0.92 (0.87-0.98), p=0.007], a response that is correlated with worse PD status. Moreover, 4 additional candidate variants were indirectly supported by associations with less frequent dental flossing [rs75933965, 1.17(1.04-1.31), p=0.008], less frequent dental visits [rs77464186, 0.82(0.75-0.91), p=0.0002], less frequent dental prophylaxis [rs67111375, 0.91(0.83-0.99), p=0.03; rs77464186, 0.80(0.72-0.89), p=3.8e-05], or having bone loss around teeth [rs8047395, 1.09(1.03-1.15), p=0.005]. Discussion: This integrative approach identified one colocalized locus and 14 additional candidate loci that are shared between T2D and PD/oral health by comparing effects across PD, T2D and BMD. Future research is needed to independently validate our findings.

Number of teeth is associated with all-cause and disease-specific mortality.

BACKGROUND: Tooth loss has been shown to correlate with multiple systemic comorbidities. However, the associations between the number of remaining natural teeth (NoT) and all-cause mortality have not been explored extensively. We aimed to investigate whether having fewer NoT imposes a higher risk in mortality. We tested such hypotheses using three groups of NoT (20-28,10-19, and 0-9), edentulism and without functional dentition (NoT < 19). METHODS: The National Health and Nutrition Examination Survey in the United States (NHANES) (1999-2014) conducted dental examinations and provided linkage of mortality data. NHANES participants aged 20 years and older, without missing information of dental examination, age, gender, race, education, income, body-mass-index, smoking, physical activities, and existing systemic conditions [hypertension, total cardiovascular disease, diabetes, and stroke (N = 33,071; death = 3978), or with femoral neck bone mineral density measurement (N = 13,131; death = 1091)] were analyzed. Cox proportional hazard survival analyses were used to investigate risks of all-cause, heart disease, diabetes and cancer mortality associated with NoT in 3 groups, edentulism, or without functional dentition. RESULTS: Participants having fewer number of teeth had higher all-cause and disease-specific mortality. In fully-adjusted models, participants with NoT0-9 had the highest hazard ratio (HR) for all-cause mortality [HR(95%CI) = 1.46(1.25-1.71); p < .001], mortality from heart diseases [HR(95%CI) = 1.92(1.33-2.77); p < .001], from diabetes [HR(95%CI) = 1.67(1.05-2.66); p = 0.03], or cancer-related mortality [HR(95%CI) = 1.80(1.34-2.43); p < .001]. Risks for all-cause mortality were also higher among the edentulous [HR(95%CI) = 1.35(1.17-1.57); p < .001] or those without functional dentition [HR(95%CI) = 1.34(1.17-1.55); p < .001]. CONCLUSIONS: Having fewer NoT were associated with higher risks for all-cause mortality. More research is needed to explore possible biological implications and validate our findings.

Number of teeth is associated with hip fracture and femoral neck bone mineral density in the NHANES.

PURPOSE/INTRODUCTION: Tooth loss has been found to be associated with fractures and osteoporosis. However, the associations between number of teeth with bone mineral density as well as with hip fractures have not been explored in the same study setting. METHODS: Data from the cross-sectional National Health and Nutrition Examination Survey (2005-2010, 2013-2014, and 2017-2018) with completed femoral neck bone mineral density (BMD) measurements, osteoporosis questionnaires, and dentition examinations were analyzed. A total of 15,198 participants, with a mean age of 53.9 and diverse ethnicity, males (52%), and females (48%), were analyzed. Multivariate logistic regression analyses for self-reported hip fractures, self-reported osteoporosis, and measured low femoral BMD accounting for traditional risk factors were tested for the total number of natural teeth (NoT) present, or by NoT in the anterior or posterior segments. RESULTS: Subjects with fewer natural teeth present were more likely to report a hip fracture, osteoporosis, or having lower levels of femoral neck BMD. With one additional tooth present in the mouth, there was a decreased association with self-reported hip fracture [OR(95%CI) = 0.98(0.96-0.99); P = 0.005] or with less likelihood of having low femoral neck BMD [OR(95%CI) = 0.99(0.97-1.00); P = 0.007]. CONCLUSIONS: With the limitation of the cross-sectional study design, results should be interpreted cautiously, yet our analyses point to an association between a decreased number of natural teeth present and self-reported hip fractures or low femoral neck BMD. The number of teeth present could be potentially utilized for assessing risks of hip fracture and osteoporosis. Future research is needed to validate our findings.

Efficacy of an Er:YAG laser in the decontamination of dental implant surfaces: An in vitro study.

BACKGROUND: Emergence of peri-implant diseases led to the development of various methods for implant surface decontamination. This study was designed to compare the efficacy of biofilm removal from implant-like titanium surfaces by an erbium-doped yttrium-aluminum-garnet (Er:YAG) laser, titanium brush, and carbon fiber curet. METHODS: Eight study subjects were recruited. A custom mouth appliance that held eight sandblasted and acid-etched titanium discs was fabricated for each subject. Subjects were asked to wear this appliance for 72 hours to allow for biofilm development. After retrieval, discs were removed and randomized to one of four treatment groups. The discs were stained with a two-component nucleic acid dye kit, and the residual biofilm was visualized under fluorescence microscopy. Quantification of residual biofilm was performed using an image analysis software and expressed as the percentage surface area. RESULTS: Fifty-nine titanium discs were randomized to the four treatment groups. The percentage of titanium disc area covered by residual biofilm was 74.0% ± 21.6%, 32.8% ± 24.0%, 11.8% ± 10.3%, and 20.1% ± 19.2% in the control, Er:YAG, titanium brush and carbon fiber curet groups, respectively (mean ± SD). The biofilm-covered area significantly decreased in each of the three treatment groups compared with control (P < 0.008). Comparisons between treatment groups did not reveal statistical significance. CONCLUSIONS: Er:YAG laser treatment is an effective method for reducing the bacterial biofilm on titanium discs. However, on a threadless titanium surface, Er:YAG laser does not exhibit a significantly greater efficacy in biofilm removal than commonly used titanium brushes or carbon fiber curets.

Identification and characterization of a novel adiponectin receptor agonist adipo anti-inflammation agonist and its anti-inflammatory effects in vitro and in vivo.

BACKGROUND AND PURPOSE: Adiponectin (APN) is an adipokine secreted from adipocytes that binds to APN receptors AdipoR1 and AdipoR2 and exerts an anti-inflammatory response through mechanisms not fully understood. There is a need to develop small molecules that activate AdipoR1 and AdipoR2 and to be used to inhibit the inflammatory response in lipopolysaccharide (LPS)-induced endotoxemia and other inflammatory disorders. EXPERIMENTAL APPROACH: We designed 10 new structural analogues of an AdipoR agonist, AdipoRon (APR), and assessed their anti-inflammatory properties. Bone marrow-derived macrophages (BMMs) and peritoneal macrophages (PEMs) were isolated from mice. Levels of pro-inflammatory cytokines were measured by reverse transcription and real-time quantitative polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA) and microarray in LPS-induced endotoxemia mice and diet-induced obesity (DIO) mice in which systemic inflammation prevails. Western blotting, immunohistochemistry (IHC), siRNA interference and immunoprecipitation were used to detect signalling pathways. KEY RESULTS: A novel APN receptor agonist named adipo anti-inflammation agonist (AdipoAI) strongly suppresses inflammation in DIO and endotoxemia mice, as well as in cultured macrophages. We also found that AdipoAI attenuated the association of AdipoR1 and APPL1 via myeloid differentiation marker 88 (MyD88) signalling, thus inhibiting activation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and c-Maf pathways and limiting the production of pro-inflammatory cytokines in LPS-induced macrophages. CONCLUSION AND IMPLICATIONS: AdipoAI is a promising alternative therapeutic approach to APN and APR to suppress inflammation in LPS-induced endotoxemia and other inflammatory disorders via distinct signalling pathways.

Volumetric Changes Following Lateral Guided Bone Regeneration.

Resorbable membranes are well described and employed for horizontal guided bone regeneration (GBR). However, the currently available literature does not provide information on the bone volumetric changes during the healing that follows GBR procedures and dental implant placement. Therefore, the aim of this pilot study was to initially analyze the volumetric bone changes after treating pristine edentulous mandibular defects with lateral GBR using freeze-dried bone allograft (FDBA) and collagen resorbable membrane. Six patients were selected for the analysis. Clinical changes in bone volume before and after GBR were measured. In addition, digital volumetric analysis of the augmented ridges was performed preoperatively, as well as 4 and 6 months after the GBR procedure. At the time of dental implant placement, bone cores were collected during the osteotomy for histologic analysis. Data on volume changes showed a mean of 297.5 ± 134 mm3 augmented bone volume at 4 months with 5% ± 3.78% resorption from 4 to ≥ 6 months. Histologic bone core analysis showed 44.9% plusmn; 5.1% mineralization in the area of augmentation. Within the limitations of this pilot study, resorbable membranes exhibited reliability for GBR in intercalated mandibular defects, providing sufficient bone volume gain at ≥ 6 months for implant stabilization and limited resorption during graft healing.

Diagnosing periodontal and dental indicators with horizontal and vertical bitewing radiographs.

OBJECTIVE: The aim of this study is to compare information provided by the 2 orientations of bitewing radiographs, horizontal (HBW) and vertical (VBW) taken in a dental school. METHODS AND MATERIALS: Radiographic records were reviewed at Tufts University School of Dental Medicine (TUSDM) for patients showing posterior bone loss who had both HBW and VBW. 320 records were reviewed with 6 criteria: visibility of crestal bone from the distal of the cuspids to the distal of the most posterior tooth, visibility of horizontal or angular bone loss, the crestal density of bone, visibility of interproximal contact areas, visibility of the entire anatomical crown, and visibility of furcations. RESULTS: Significantly higher number of VBW compared with HBW (P < 0.0001) showed the levels of alveolar bone loss (52.81% vs. 3.75%), the type of loss (angular or horizontal) (50.94% vs. 3.75%), the crestal bone density (28.75% vs. 0.63%), the contact areas (20.63% vs. 14.38%), and the furcations (43.44% vs. 1.25%). A greater number of HBW showed the entire anatomical crown compared with VBW. No significant difference was detected in the number of radiographs taken per HBW and VBW set. CONCLUSION: For patients with alveolar bone loss, VBW are superior to HBW when assessing bone levels, density, morphology, tooth furcations, and evaluating interproximal contact areas for caries. It is recommended that the vertical bitewing technique be taught as a standard in dental, dental hygiene, and dental assisting schools for adult patients showing evidence of posterior interdental bone loss.

Potential roles of miR-335-5p on pathogenesis of experimental periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is a prevalent oral disease responsible for tooth loss. MicroRNAs have been proven crucial in bone disorders over the past decades. Promotive effect on osteogenic activities by microRNA-335-5p (miR-335-5p) has been well demonstrated, but its role involved in the pathogenesis of periodontitis remains elusive. In this study, we established experimental periodontitis (EP) on transgenic mice overexpressing miR-335-5p (335-Tg) to investigate the novel effects of miR-335-5p on periodontal inflammation and bone loss. METHODS: Experimental periodontitis was established via ligation. The expression of inflammatory and osteoclastic genes was examined by quantitative real-time PCR (qPCR). Morphology of alveolar bone was analyzed by microcomputed tomography (µCT). Hematoxylin and eosin (H&E), tartrate-resistant acid phosphatase (TRAP), and Toll-like receptor 4 (TLR4) immunohistochemistry (IHC) staining were conducted for histological analysis. RESULTS: The expression of miR-335-5p decreased significantly in the periodontal tissues of EP. Compared to the WT-EP group, µCT analysis showed less bone loss in the 335-Tg-EP group accompanying with a decreased number of TRAP-positive osteoclasts. H&E and IHC staining exhibited attenuated inflammation and TLR4 expression in the 335-Tg-EP group. Furthermore, reduced expressions of IL-1ß, IL-6, TNF-α, and TLR4 were also detected in the 335-Tg-EP group. Overexpression of miR-335-5p in vivo weakened the periodontal bone destruction and inflammation compared with the WT-EP group. CONCLUSIONS: Our data exhibit novel roles of miR-335-5p in preventing bone loss and inflammation in experimental periodontitis.

A Comparison between Primary and Secondary Flap Coverage in Ridge Preservation Procedures: A Pilot Randomized Controlled Clinical Trial.

AIMS: To assess the bone dimensional changes after extraction and alveolar ridge preservation (ARP) using primary coverage (closed flap technique, CFT) or healing by secondary intention (open flap technique, OFT). MATERIALS AND METHODS: Ten patients (split mouth design) were planned for extraction and ARP. All sites received ARP with freeze-dried bone allograft (FDBA) and nonresorbable membrane after extraction. Clinical standardized measurements were used to assess the dimensional alterations of the alveolar ridge. RESULTS: All patients completed the study, and a total of 20 sites were randomized to CFT or OFT group. Center height (mean difference of 8.1 mm, SD =1.9 CFT, and 7.5 mm, SD= 1.8 OFT) and buccal height (mean difference of 0.8 mm, SD =1.0 CFT, and 0.3 mm, SD= 1.1 OFT) were significantly different within the same group. However, there was no statistically significant difference between groups. In the OFT group, the keratinized tissue width was higher and the pain VAS scores at 24 hours were lower compared with the CFT (p = 0.004 and p = 0.006, respectively). CONCLUSIONS: Leaving the flap open did not have any effects on the dimensional changes of bone height or width. However, there was a wider band of keratinized tissue and less pain with the CFT compared with the OFT. The study protocol was registered at ClinicalTrials.gov, Identifier NCT03136913.

Association between time since quitting smoking and periodontitis in former smokers in the National Health and Nutrition Examination Surveys (NHANES) 2009 to 2012.

BACKGROUND: The aims of this study were to analyze the periodontal conditions among non-smokers, former smokers and current smokers in the two National Health and Nutrition Examination Surveys (NHANES) acquired between 2009 to 2012 and determine the association between time since quitting smoking and periodontal status. METHODS: Smoking status and periodontal examination data from NHANES 2009 to 2010 and 2011 to 2012 were analyzed. Respondents included in the analysis were aged ≥18 years, had undergone a complete NHANES Oral Health - Periodontal Exam with all measurements recorded as required for the periodontal classification algorithm, and had complete data from the NHANES Smoking - Cigarette Use questionnaire. Logistic regression was conducted with time since quitting as the exposure and presence of periodontitis as the outcome, and included adjustment for confounders. RESULTS: Smoking status was significantly associated with periodontal status (Chi-square; P < 0.0001). The rate of periodontitis was highest among smokers (35%), compared with former smokers (19%) and never smokers (13%). Among former smokers, after adjusting for confounders, each additional year since quitting smoking was associated with a significant reduction in the odds ratio (OR) for periodontitis by 3.9% (OR for each year 0.961, 95% confidence interval 0.948 to 0.975). CONCLUSIONS: Among former smokers, a longer time since quitting smoking was associated with a lower likelihood of periodontitis. Consequently, dental practitioners have a public health mandate to help their patients quit smoking. Future research should determine the best strategies for facilitating smoking cessation in dental patients.

Prospective study of the impact of peri-implant soft tissue properties on patient-reported and clinically assessed outcomes.

BACKGROUND: It has been proposed that the presence of a zone of keratinized mucosa (KM) around implants is associated with less discomfort during brushing and improved esthetic outcomes. Therefore, mucogingival procedures have been recommended for patients with discomfort during brushing, and to enhance esthetic results around implants without KM. However, no study has systematically assessed and compared discomfort during brushing, patient soft tissue esthetic satisfaction, and other clinical parameters between implants with and without KM. METHODS: Group 1 included patients with implants surrounded by KM, whereas patients in Group 2 had no KM around implants. Patient discomfort during brushing and esthetic satisfaction were measured with a visual analog scale and compared between the 2 groups using a mixed model. Clinical width of KM, probing depth, peri-implant recession, plaque index, and bleeding on probing were compared within and between groups 3 and 6 months following implant restoration. RESULTS: Twenty-four patients (12 in each group) were evaluated at the 3- and 6-month follow-up visits. Patients without peri-implant KM were less satisfied with the esthetics of the soft tissue around their implants (P < 0.01). However, lack of KM was not associated with discomfort during brushing. In Group 1, width of KM was significantly increased after 6 months (P < 0.01). There was greater recession around implants without KM after 3 months (P < 0.01), but not after 6 months. CONCLUSIONS: Patients reported that presence or absence of keratinized mucosa did not affect discomfort associated with brushing. Yet, esthetically, patients preferred implants with a zone of keratinized mucosa.

Second Generation Triple-Helical Peptide Inhibitors of Matrix Metalloproteinases.

The design of selective matrix metalloproteinase (MMP) inhibitors that also possess favorable solubility properties has proved to be especially challenging. A prior approach using collagen-model templates combined with transition state analogs produced a first generation of triple-helical peptide inhibitors (THPIs) that were effective in vitro against discrete members of the MMP family. These THPI constructs were also highly water-soluble. The present study sought improvements in the first generation THPIs by enhancing thermal stability and selectivity. A THPI selective for MMP-2 and MMP-9 was redesigned to incorporate non-native amino acids (Flp and mep), resulting in an increase of 18 °C in thermal stability. This THPI was effective in vivo in a mouse model of multiple sclerosis, reducing clinical severity and weight loss. Two other THPIs were developed to be more selective within the collagenolytic members of the MMP family. One of these THPIs was serendipitously more effective against MMP-8 than MT1-MMP and was utilized successfully in a mouse model of sepsis. The THPI targeting MMP-8 minimized lung damage, increased production of the anti-inflammatory cytokine IL-10, and vastly improved mouse survival.

Efficacy of collagen matrix seal and collagen sponge on ridge preservation in combination with bone allograft: A randomized controlled clinical trial.

AIM: To test whether the use of collagen matrix seal (CMS) results in similar hard and soft tissue remodelling to that with collagen sponge (CS) used as barriers 4 months following alveolar ridge preservation (ARP), in combination with freeze-dried bone allograft (FDBA). MATERIALS AND METHODS: Twenty-eight patients were randomly assigned to the two groups. Clinical and radiographic measurements were recorded with the same stent at baseline and 4 months for standardization. The flapless technique following a traumatic extraction was used for the two types of barriers. RESULTS: All patients completed the study, 14 in the CMS group and 14 in the CS group. Reduction in coronal ridge width (1.21 mm-14.91% CMS and 1.47 mm-20.40% CS) and vertical buccal bone resorption (0.30 mm CMS and 0.79 mm CS) were not significantly different. A slight increase in buccal gingival thickness at the coronal part was observed in both groups (0.9 mm CMS and 0.5 mm CS). CONCLUSIONS: Collagen matrix seal and CS, when combined with FDBA, significantly minimized ridge resorption in all dimensions and maintained buccal soft tissue thickness in sockets with a buccal plate loss of <2 mm in comparison to previously reported findings recorded after tooth extraction without ARP.

Prospective Clinical and Radiographic Study of Alveolar Ridge Preservation Combining Freeze-Dried Bone Allograft With Two Xenogeneic Collagen Matrices.

BACKGROUND: Tooth extractions are followed by significant dimensional changes in the alveolar crest that may preclude implant placement. This randomized, controlled, prospective compares the preservation of soft and hard tissue dimensional changes after alveolar ridge preservation (ARP) using two membranes consisting of collagen matrix (CM) or extracellular matrix (ECM) as barriers over freeze-dried bone allograft (FDBA). METHODS: Standardized clinical and radiographic measurements of soft and hard tissues were recorded by means of a stent before and 4 months after ARP. The surgery entailed sulcular incisions with minimal flap elevation and repositioning without advancement. RESULTS: Of 11 patients in the CM group and 12 in the ECM group who completed the study, gingival thickness (GT) increased from 0.1 to 0.2 mm for both groups along with a 0.5-mm decrease in the width of keratinized tissue after healing. Reductions in ridge width were most pronounced on the coronal aspect, 1.8 mm for CM and 2.0 mm for ECM, whereas vertical reduction was most pronounced on the buccal aspect, 0.7 to 1.0 mm. Differences between groups were not statistically significant. However, significant correlation for changes in GT (P = 0.001) and crestal bone width (P = 0.002) with preoperative buccal plate thickness (BPT) was observed. CONCLUSIONS: Both xenogeneic collagen matrices combined with FDBA were effective in maintaining soft tissues and minimizing ridge resorption in all dimensions after ARP. BPT was an important determinant for amount of change in crestal GT and ridge width.

Using a Simulated Infobutton Linked to an Evidence-Based Resource to Research Drug-Drug Interactions: A Pilot Study with Third-Year Dental Students.

Many health professions students and clinicians are using evidence-based databases that allow for quicker and more accurate clinical decisions. The aims of this pilot study were to compare third-year dental students' speed and accuracy in researching questions about drug-drug interactions (DDI) when using two different methods: a simulated infobutton linked to the evidence-based clinical decision support resource UpToDate versus traditional Internet resources accessed through a computer or smart device. Students researched two simulated cases during two sessions. In the first session, half the students used the infobutton, while the other half used traditional electronic tools only. In the second session, ten days later, a cross-over took place. The sessions were timed, and after researching the case, students answered three questions on the use of antibiotics, analgesics, and local anesthetics. Of the 50 students who volunteered for the study, two were excluded, and 44 participated in both sessions and the exam. The results showed that the students took a similar amount of time to identify DDI whether they used the infobutton (mean=286.5 seconds) or traditional tools (265.2 seconds); the difference was not statistically significant (p=0.429). Their scores using the two research methods were similar in all three content areas: antibiotics (p=0.797), analgesics (p=0.850), and local anesthetics (p=0.850). In a post-intervention survey, students were generally favorable about infobutton and UpToDate, reporting the tool was easy to use (62.5%), provided the answer they were looking for (53.1%), was fast (50%), and they would use it again (68.8%). This pilot study found that the time and accuracy of these students conducting DDI research with the infobutton and UpToDate were about the same as using traditional Internet resources.

Fibronectin-binding protein TDE1579 affects cytotoxicity of Treponema denticola.

While FbpA, a family of bacterial fibronectin (FN) binding proteins has been studied in several gram-positive bacteria, the gram-negative Treponema denticola, an anaerobic periodontal pathogen, also has an overlooked fbp gene (tde1579). In this research, we confirm that recombinant Fbp protein (rFbp) of T. denticola binds human FN with a Kdapp of 1.5 × 10(-7) M and blocks the binding of T. denticola to FN in a concentration-dependent manner to a level of 42%. The fbp gene was expressed in T. denticola. To reveal the roles of fbp in T. denticola pathogenesis, an fbp isogenic mutant was constructed. The fbp mutant had 51% reduced binding ability to human gingival fibroblasts (hGF). When hGF were challenged with T. denticola, the fbp mutant caused less cell morphology change, had 50% reduced cytotoxicity to hGF, and had less influence on the growth of hGF cells.

Identification of collagen binding domain residues that govern catalytic activities of matrix metalloproteinase-2 (MMP-2).

An innovative approach to enhance the selectivity of matrix metalloproteinase (MMP) inhibitors comprises targeting these inhibitors to catalytically required substrate binding sites (exosites) that are located outside the catalytic cleft. In MMP-2, positioning of collagen substrate molecules occurs via a unique fibronectin-like domain (CBD) that contains three distinct modular collagen binding sites. To characterize the contributions of these exosites to gelatinolysis by MMP-2, seven MMP-2 variants were generated with single, or concurrent double and triple alanine substitutions in the three fibronectin type II modules of the CBD. Circular dichroism spectroscopy verified that recombinant MMP-2 wild-type (WT) and variants had the same fold. Moreover, the MMP-2 WT and variants had the same activity on a short FRET peptide substrate that is hydrolyzed independently of CBD binding. Among single-point variants, substitution in the module 3 binding site had greatest impact on the affinity of MMP-2 for gelatin. Simultaneous substitutions in two or three CBD modules further reduced gelatin binding. The rates of gelatinolysis of MMP-2 variants were reduced by 20-40% following single-point substitutions, by 60-75% after double-point modifications, and by >90% for triple-point variants. Intriguingly, the three CBD modules contributed differentially to cleavage of dissociated α-1(I) and α-2(I) collagen chains. Importantly, kinetic analyses (k(cat)/K(m)) revealed that catalysis of a triple-helical FRET peptide substrate by MMP-2 relied primarily on the module 3 binding site. Thus, we have identified three collagen binding site residues that are essential for gelatinolysis and constitute promising targets for selective inhibition of MMP-2.

Binding of amelogenin to MMP-9 and their co-expression in developing mouse teeth.

Amelogenin is the most abundant matrix protein in enamel. Proper amelogenin processing by proteinases is necessary for its biological functions during amelogenesis. Matrix metalloproteinase 9 (MMP-9) is responsible for the turnover of matrix components. The relationship between MMP-9 and amelogenin during tooth development remains unknown. We tested the hypothesis that MMP-9 binds to amelogenin and they are co-expressed in ameloblasts during amelogenesis. We evaluated the distribution of both proteins in the mouse teeth using immunohistochemistry and confocal microscopy. At postnatal day 2, the spatial distribution of amelogenin and MMP-9 was co-localized in preameloblasts, secretory ameloblasts, enamel matrix and odontoblasts. At the late stages of mouse tooth development, expression patterns of amelogenin and MMP-9 were similar to that seen in postnatal day 2. Their co-expression was further confirmed by RT-PCR, Western blot and enzymatic zymography analyses in enamel organ epithelial and odontoblast-like cells. Immunoprecipitation assay revealed that MMP-9 binds to amelogenin. The MMP-9 cleavage sites in amelogenin proteins across species were found using bio-informative software program. Analyses of these data suggest that MMP-9 may be involved in controlling amelogenin processing and enamel formation.