Effect of Periodontal Treatment on Reducing Chronic Inflammation in Systemically Healthy Patients With Periodontal Disease.

BACKGROUND: We determined the effects and an accurate marker of periodontal treatment on serum interleukin (IL)-6 and high-sensitivity C-reactive protein (HsCRP) levels in systemically healthy individuals with periodontal disease. METHODS: This multicenter study included systemically healthy individuals with periodontal disease who received initial periodontal treatment and had no periodontal treatment history. Periodontal parameters, including periodontal inflamed surface area, masticatory efficiency, and periodontal disease classification; serum IL-6 and HsCRP levels; and serum immunoglobulin (Ig)G titers against periodontal pathogens were evaluated at baseline and after treatment. Subjects were classified as low or high responders (group) based on periodontal inflamed surface area changes. RESULTS: There were 153 participants. Only periodontal inflamed surface area changes were markedly different between low and high responders. Periodontal treatment (time point) decreased both serum IL-6 and HsCRP levels. The interaction between group and time point was remarkable only for serum IL-6 levels. Changes in serum immunoglobulin (Ig)G titers against periodontal pathogens were not associated with IL-6 changes in high responders. We analyzed the indirect effect of serum anti-Porphyromonas gingivalis type 2 IgG titer changes using mediation analysis and found no significance. However, the direct effect of group (low or high responder) on IL-6 changes was considerable. CONCLUSIONS: Periodontal treatment effectively decreased serum IL-6 levels, independent of periodontal pathogen infection, in systemically healthy individuals with periodontal disease.

Profile of Nagasaki Islands Study (NaIS): A Population-Based Prospective Cohort Study on Multi-disease.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014-2016, secondary surveys during 2017-2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27-96 and 28-98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Clinical Efficacy and Safety of Antimicrobial Photodynamic Therapy in Residual Periodontal Pockets during the Maintenance Phase.

Antimicrobial photodynamic therapy (a-PDT) in combination with scaling root planing (SRP) is more effective at improving periodontal status than SRP alone. However, the effectiveness of a-PDT in combination with irrigation for patients undergoing periodontal maintenance has not been clarified. This study evaluated the efficacy and safety of a-PDT in the maintenance phase. Patients who had multiple sites with bleeding on probing (BOP) and periodontal probing depth (PPD) of 4-6 mm in the maintenance phase were treated with a split-mouth design. These sites were randomly assigned to one of two groups: the a-PDT group and the irrigation group. In the a-PDT group, the periodontal pockets were treated with light-sensitive toluidine blue and a light irradiator. In the irrigation group, the periodontal pockets were simply irrigated using an ultrasonic scaler. After 7 days, the safety and efficacy of a-PDT were assessed. The mean PPD of the a-PDT group had reduced from 4.50 mm to 4.13 mm, whereas negligible change was observed in the irrigation group. BOP significantly improved from 100% to 33% in the PDT group, whereas it hardly changed in the irrigation group. No adverse events were observed in any patients. a-PDT may be useful as a noninvasive treatment in the maintenance phase, especially in patients with relatively deep periodontal pocket.

The efficacy of a novel zinc-containing desensitizer CAREDYNE Shield for cervical dentin hypersensitivity: a pilot randomized controlled trial.

BACKGROUND: Recently, a novel zinc-containing desensitizer, CAREDYNE Shield, was developed. This new type of desensitizer induces chemical occlusion of dentinal tubules for desensitization and releases zinc ion for root caries prevention. Despite these features, its clinical effectiveness in the improvement of cervical dentine hypersensitivity remains to be elucidated. Thus, we aimed to evaluate the effectiveness of CAREDYNE Shield in patients with CDH. METHODS: Forty CDH teeth which matched the eligibility criteria were randomly allocated to two groups in a 1:1 ratio: the CAREDYNE Shield group (intervention group) and the Nanoseal group (control group). The pain intensity in response to air stimuli, gingival condition, and oral hygiene status of CDH teeth were assessed before and at 4 weeks after treatment. The primary outcome was the reduction of pain intensity in response to air stimuli from baseline to 4 weeks after intervention. RESULTS: From November 2019 to April 2021, 24 participants with 40 teeth were enrolled in this study and 33 teeth in 20 participants were assessed at 4 weeks after treatment. A significant reduction of pain in response to air stimuli was observed in both groups; however, no significant difference was observed between the groups. CONCLUSIONS: This study showed that CAREDYNE Shield is effective for CDH and its effectiveness is similar to Nanoseal. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000038072. Registered on 21st September 2019, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043331.

NLRP3 Inflammasome Negatively Regulates RANKL-Induced Osteoclastogenesis of Mouse Bone Marrow Macrophages but Positively Regulates It in the Presence of Lipopolysaccharides.

In inflammatory bone diseases such as periodontitis, the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome accelerates bone resorption by promoting proinflammatory cytokine IL-1ß production. However, the role of the NLRP3 inflammasome in physiological bone remodeling remains unclear. Here, we investigated its role in osteoclastogenesis in the presence and absence of lipopolysaccharide (LPS), a Gram-negative bacterial component. When bone marrow macrophages (BMMs) were treated with receptor activator of nuclear factor-κB ligand (RANKL) in the presence of NLRP3 inflammasome inhibitors, osteoclast formation was promoted in the absence of LPS but attenuated in its presence. BMMs treated with RANKL and LPS produced IL-1ß, and IL-1 receptor antagonist inhibited osteoclastogenesis, indicating IL-1ß involvement. BMMs treated with RANKL alone produced no IL-1ß but increased reactive oxygen species (ROS) production. A ROS inhibitor suppressed apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) speck formation and NLRP3 inflammasome inhibitors abrogated cytotoxicity in BMMs treated with RANKL, indicating that RANKL induces pyroptotic cell death in BMMs by activating the NLRP3 inflammasome via ROS. This suggests that the NLRP3 inflammasome promotes osteoclastogenesis via IL-1ß production under infectious conditions, but suppresses osteoclastogenesis by inducing pyroptosis in osteoclast precursors under physiological conditions.

Cytotoxic effects of dental calculus particles and freeze-dried Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum on HSC-2 oral epithelial cells and THP-1 macrophages.

BACKGROUND: Periodontitis is an inflammatory disease initiated by dental deposits. Microorganisms in the dental biofilm induce cell death in epithelial cells, contributing to the breakdown of epithelial barrier function. Recently, dental calculus has also been implicated in pyroptotic cell death in oral epithelium. We analyzed the cytotoxic effects of dental calculus and freeze-dried periodontopathic bacteria on oral epithelial cells and macrophages. METHODS: HSC-2 (human oral squamous carcinoma cells) and phorbol 12-myristate 13-acetate-differentiated THP-1 macrophages were exposed to dental calculus or one of two species of freeze-dried bacterium, Aggregatibacter actinomycetemcomitans and Fusobacterium nucleatum. Following incubation for 24 hours, we measured cytotoxicity via lactate dehydrogenase release. Cells were then incubated with glyburide, an NLRP3 inflammasome inhibitor, to assess the potential role of pyroptosis. We also conducted a permeability assay to analyze the effects on epithelial barrier function. RESULTS: Dental calculus induced dose-dependent cell death in HSC-2 cells, whereas cell death induced by freeze-dried bacteria was insignificant. Conversely, freeze-dried bacteria induced more cell death than dental calculus in THP-1 macrophages. Cell death induced by dental calculus but not by freeze-dried bacteria was inhibited by glyburide, indicating that these are different types of cell death. In the permeability assays, dental calculus but not freeze-dried bacteria attenuated the barrier function of HSC-2 cell monolayers. CONCLUSION: Due to the low sensitivity of HSC-2 cells to microbial cytotoxicity, dental calculus had stronger cytotoxic effects on HSC-2 cell monolayers than freeze-dried A. actinomycetemcomitans and F. nucleatum, suggesting that it plays a critical role in the breakdown of crevicular/pocket epithelium integrity.

The Role of Cytokines Produced via the NLRP3 Inflammasome in Mouse Macrophages Stimulated with Dental Calculus in Osteoclastogenesis.

Dental calculus (DC) is a common deposit in periodontitis patients. We have previously shown that DC contains both microbial components and calcium phosphate crystals that induce an osteoclastogenic cytokine IL-1ß via the NLRP3 inflammasome in macrophages. In this study, we examined the effects of cytokines produced by mouse macrophages stimulated with DC on osteoclastogenesis. The culture supernatants from wild-type (WT) mouse macrophages stimulated with DC accelerated osteoclastogenesis in RANKL-primed mouse bone marrow macrophages (BMMs), but inhibited osteoclastogenesis in RANKL-primed RAW-D cells. WT, but not NLRP3-deficient, mouse macrophages stimulated with DC produced IL-1ß and IL-18 in a dose-dependent manner, indicating the NLRP3 inflammasome-dependent production of IL-1ß and IL-18. Both WT and NLRP3-deficient mouse macrophages stimulated with DC produced IL-10, indicating the NLRP3 inflammasome-independent production of IL-10. Recombinant IL-1ß accelerated osteoclastogenesis in both RANKL-primed BMMs and RAW-D cells, whereas recombinant IL-18 and IL-10 inhibited osteoclastogenesis. These results indicate that DC induces osteoclastogenic IL-1ß in an NLRP3 inflammasome-dependent manner and anti-osteogenic IL-18 and IL-10 dependently and independently of the NLRP3 inflammasome, respectively. DC may promote alveolar bone resorption via IL-1ß induction in periodontitis patients, but suppress resorption via IL-18 and IL-10 induction in some circumstances.

Functional roles of fish collagen peptides on bone regeneration.

Fish collagen peptides (FCP) derived from the skin, bones and scales are commercially used as a functional food or dietary supplement for hypertension and diabetes. However, there is limited evidence on the effects of FCP on the osteoblast function in contrast to evidence of the effects on wound healing, diabetes and bone regeneration, which have been obtained from animal studies. In this narrative review, we expound on the availability of FCP by basic research using osteoblasts. Low-concentration FCP upregulates the expression of osteoblast proliferation, differentiation and collagen modifying enzyme-related genes. Furthermore, it could accelerate matrix mineralization. FCP may have potential utility as a biomaterial to improve collagen quality and promote mineralization through the mitogen-activated protein kinase and Smad cascades. However, there are few clinical studies on bone regeneration in human subjects. It is desirable to be applied clinically through clinical study as soon as possible, based on the results from basic research.

Prospective Longitudinal Changes in the Periodontal Inflamed Surface Area Following Active Periodontal Treatment for Chronic Periodontitis.

Periodontal disease is a chronic inflammatory disease of the periodontal tissue. The periodontal inflamed surface area (PISA) is a proposed index for quantifying the inflammatory burden resulting from periodontitis lesions. This study aimed to investigate longitudinal changes in the periodontal status as evaluated by the PISA following the active periodontal treatment. To elucidate the prognostic factors of PISA, mixed-effect modeling was performed for clinical parameters, tooth-type, and levels of periodontal pathogens as independent variables. One-hundred-twenty-five patients with chronic periodontitis who completed the active periodontal treatment were followed-up for 24 months, with evaluations conducted at 6-month intervals. Five-times repeated measures of mean PISA values were 130+/-173, 161+/-276, 184+/-320, 175+/-417, and 209+/-469 mm2. Changes in clinical parameters and salivary and subgingival periodontal pathogens were analyzed by mixed-effect modeling. Plaque index, clinical attachment level, and salivary levels of Porphyromonas gingivalis were associated with changes in PISA at the patient- and tooth-level. Subgingival levels of P. gingivalis and Prevotella intermedia were associated with changes in PISA at the sample site. For most patients, changes in PISA were within 10% of baseline during the 24-month follow-up. However, an increase in the number of bleeding sites in a tooth with a deep periodontal pocket increased the PISA value exponentially.

Estimation of the Periodontal Inflamed Surface Area by Simple Oral Examination.

The periodontal inflamed surface area (PISA) is a useful index for clinical and epidemiological assessments, since it can represent the inflammation status of patients in one contentious variable. However, calculation of the PISA is difficult, requiring six point probing depth measurements with or without bleeding on probing on 28 teeth, followed by data input in a calculation program. More simple methods are essential for screening periodontal disease or in epidemiological studies. In this study, we tried to establish a convenient partial examination method to estimate PISA. Cross-sectional data of 254 subjects who completed active periodontal therapy were analyzed. Teeth that represent the PISA value were selected by an item response theory approach. The maxillary second molar, first premolar, and lateral incisor and the mandibular second molar and lateral incisor were selected. The sum of the PISAs of these teeth was significantly correlated with the patient's PISA (R2 = 0.938). More simply, the sum of the maximum values of probing pocket depth with bleeding for these teeth were also significantly correlated with the patient's PISA (R2 = 0.6457). The simple model presented in this study may be useful to estimate PISA.

Expression of osteoclastogenic and anti-osteoclastogenic cytokines differs in mouse gingiva injected with lipopolysaccharide, peptidoglycan, or both.

OBJECTIVE: Bacterial substances in subgingival biofilm evoke alveolar bone resorption. We previously reported that gingival injection of bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) induced alveolar bone resorption in mice. However, the mechanism by which LPS and PGN induce osteoclast formation has not been investigated. The aim of this study is to clarify the role of osteoclastogenic and anti-osteoclastogenic cytokines in the alveolar bone resorption induced by LPS and PGN. MATERIALS: LPS from Escherichia coli, PGN from Staphylococcus aureus, or both were injected into the gingiva of mice every 48 h for a total of 13 times. Alveolar bone resorption was assessed histochemically by tartrate-resistant acid phosphatase staining. Expression of the receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor (TNF)-α, interleukin (IL)-17, and IL-10 were analyzed by immunostaining. To analyze the role of these cytokines, RANKL-pretreated mouse bone marrow macrophages were stimulated with LPS, PGN, or LPS + PGN with or without anti-TNF-α antibody, IL-17, or IL-10. RESULTS: Alveolar bone resorption was induced by both LPS and PGN and exacerbated by LPS + PGN. LPS induced higher RANKL expression than PGN. Expression of TNF-α and IL-10 was correlated with bone resorption. PGN injections induced the strongest expression of IL-17, followed by LPS + PGN and LPS. In an in vitro osteoclastogenesis assay, anti-TNF-α antibody and IL-10 inhibited osteoclast formation, but IL-17 promoted it. CONCLUSION: LPS, PGN, or LPS + PGN injections induce distinctive expression of TNF-α, IL-10, and IL-17, suggesting that the composition of these bacterial ligands in dental plaque is critical for alveolar bone resorption.

High-mobility group box 1 released by traumatic occlusion accelerates bone resorption in the root furcation area in mice.

BACKGROUND AND OBJECTIVE: Traumatic occlusion can cause bone resorption without bacterial infection. Although bone resorption in periodontitis has been relatively well studied, little is known about bone resorption by traumatic occlusion. High-mobility group box 1 (HMGB1) is released from damaged tissue and has been recently shown to promote bone resorption in a murine periodontitis model and may also promote bone resorption by traumatic occlusion. The present study aimed to examine whether HMGB1 accelerates bone resorption by traumatic occlusion in mice. MATERIALS AND METHODS: Occlusal trauma was induced in the lower left first molar of mice by bonding a wire to the upper left first molar, and bone resorption and osteoclast formation were evaluated histochemically. The expression of HMGB1, Toll-like receptor 4 (TLR4; the receptor for HMGB1), and receptor activator of NFκB ligand (RANKL; an essential osteoclast differentiation factor) was evaluated immunohistologically. In addition, mice were administrated with an anti-HMGB1-neutralizing antibody to analyze the role of HMGB1. RESULTS: Bone resorption and osteoclast formation gradually increased until day 5 at the furcation area after the application of traumatic occlusion. Expression of HMGB1 was observed at the furcation area on day 1, but was attenuated by day 3. Expression of RANKL gradually increased until day 3, but was attenuated by day 5. Administration of anti-HMGB1 antibody significantly reduced the number of osteoclasts and the expression of RANKL and TLR4 at the furcation area. CONCLUSION: Release of HMGB1 in the root furcation area accelerated bone resorption by up-regulating RANKL and TLR4 expression in mice with traumatic occlusion.

Long-term clinical and radiographic evaluation of the effectiveness of direct pulp capping materials: A meta-analysis.

The aim of this review is to evaluate the long-term effectiveness of calcium silicate-based cement (CS) and calcium hydroxide (CH) for direct pulp capping (DPC) to human pulp-exposed permanent teeth. An electronic search and manual search were performed on 21 June 2019. Long-term clinical and radiographic evaluations of the effectiveness of CS and CH for DPC to human pulp-exposed teeth were included, and data extraction, risk-of-bias assessment and meta-analyses were performed. From 645 identified articles, 7 articles met the eligibility criteria. The meta-analyses comparing CS with CH and Biodentine with mineral trioxide aggregates (MTA) on DPC success rate were performed, and significant difference was observed between CS and CH (risk ratio=1.20; p=0.005), whereas no significant difference was observed between Biodentine and MTA. CS seems to be a more effective and predictable DPC material than CH; however, these analyses are based on the studies judged at high risk of bias.

A multicenter prospective cohort study on the effect of smoking cessation on periodontal therapies in Japan.

Few prospective studies have reported the effects of periodontal therapy on patients who attempted to quit smoking. This study aimed to assess how smoking cessation affects periodontal therapy. Twenty-five smokers with periodontitis were investigated by dividing them into two groups, a smoking cessation support group and a continued smoking group. Those in the support group received counseling and nicotine replacement therapy, followed by periodontal treatment conducted by dentists who had completed an e-learning course on smoking cessation. Clinical parameters were measured at baseline, 3, and 6 months. Most clinical parameters improved for those in the smoking cessation support group. There were no significant improvements in bleeding on probing (BOP) or the number of severe periodontal disease sites in the continued smoking group. Probing pocket depth (PPD) and clinical attachment levels (CAL) at sites that received scaling and root planing (SRP) significantly improved in all subjects. BOP did not improve at reevaluation in the smoking relapse subgroup. Patients in the smoking cessation support program led by dental professionals showed more improvement in BOP than those in the continued smoking group.

Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model.

Periodontal examination data have a complex structure. For epidemiological studies, mass screenings, and public health use, a simple index that represents the periodontal condition is necessary. Periodontal indices for partial examination of selected teeth have been developed. However, the selected teeth vary between indices, and a justification for the selection of examination teeth has not been presented. We applied a graded response model based on the item response theory to select optimal examination teeth and sites that represent periodontal conditions. Data were obtained from 254 patients who participated in a multicenter follow-up study. Baseline data were obtained from initial follow-up. Optimal examination sites were selected using item information calculated by graded response modeling. Twelve sites-maxillary 2nd premolar (palatal-medial), 1st premolar (palatal-distal), canine (palatal-medial), lateral incisor (palatal-central), central incisor (palatal-distal) and mandibular 1st premolar (lingual, medial)-were selected. Mean values for clinical attachment level, probing pocket depth, and bleeding on probing by full mouth examinations were used for objective variables. Measuring the clinical parameters of these sites can predict the results of full mouth examination. For calculating the periodontal index by partial oral examination, a justification for the selection of examination sites is essential. This study presents an evidence-based partial examination methodology and its modeling.

Initial periodontal treatment affects nucleotide-binding domain leucine-rich repeat-containing protein 3 inflammasome priming in peripheral blood mononuclear cells.

OBJECTIVE: Accumulating evidence suggests an association between periodontitis and several systemic diseases, such as atherosclerosis. In the lesions of these diseases, nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) and caspase-1 form inflammasome complex, which leads to the functional maturation of interleukin (IL)-1ß via cleavage of caspase-1 in macrophages. IL-1ß plays a critical role in the etiology of these diseases; however, inflammasome priming-specifically, IL-1ß and NLRP3 upregulation-is necessary for effective IL-1ß production. We investigated the effect of initial periodontal treatment on the inflammasome priming of peripheral blood mononuclear cells (PBMCs). METHODS: Twenty-two patients with chronic periodontitis were enrolled in this study and given initial periodontal treatment. Peripheral blood samples were collected at baseline and re-evaluation (41.1 ± 29.1 d after the treatment), and the relative expression of IL-1ß, and three inflammasome components, ASC, NLRP3 and Caspase-1, mRNA was determined using quantitative reverse transcription PCR. PBMCs were stimulated with silica crystals, and the IL-1ß secretion was measured via enzyme-linked immunosorbent assay. RESULTS: Probing pocket depth and bleeding on probing (BOP) were significantly improved after the treatment. Expression of IL-1ß and ASC in the PBMCs decreased after the treatment. PBMCs stimulated with silica crystals secreted IL-1ß. The treatment attenuated IL-1ß secretion by PBMCs in low BOP percentages group whereas IL-1ß secretion was increased in high BOP percentages group. CONCLUSION: Periodontal treatment altered the inflammasome priming status of the PBMCs, however, the effects on systemic diseases need to be further investigated.

Periodontal Disease in Patients Receiving Dialysis.

Chronic kidney disease (CKD) is characterized by kidney damage with proteinuria, hematuria, and progressive loss of kidney function. The final stage of CKD is known as end-stage renal disease, which usually indicates that approximately 90% of normal renal function is lost, and necessitates renal replacement therapy for survival. The most widespread renal replacement therapy is dialysis, which includes peritoneal dialysis (PD) and hemodialysis (HD). However, despite the development of novel medical instruments and agents, both dialysis procedures have complications and disadvantages, such as cardiovascular disease due to excessive blood fluid and infections caused by impaired immunity. Periodontal disease is chronic inflammation induced by various pathogens and its frequency and severity in patients undergoing dialysis are higher compared to those in healthy individuals. Therefore, several investigators have paid special attention to the impact of periodontal disease on inflammation-, nutrient-, and bone metabolism-related markers; the immune system; and complications in patients undergoing dialysis. Furthermore, the influence of diabetes on the prevalence and severity of manifestations of periodontal disease, and the properties of saliva in HD patients with periodontitis have been reported. Conversely, there are few reviews discussing periodontal disease in patients with dialysis. In this review, we discuss the available studies and review the pathological roles and clinical significance of periodontal disease in patients receiving PD or HD. In addition, this review underlines the importance of oral health and adequate periodontal treatment to maintain quality of life and prolong survival in these patients.

Pathological Characteristics of Periodontal Disease in Patients with Chronic Kidney Disease and Kidney Transplantation.

Chronic kidney disease (CKD) is recognized as an irreversible reduction of functional nephrons and leads to an increased risk of various pathological conditions, including cardiovascular disease and neurological disorders, such as coronary artery calcification, hypertension, and stroke. In addition, CKD patients have impaired immunity against bacteria and viruses. Conversely, kidney transplantation (KT) is performed for patients with end-stage renal disease as a renal replacement therapy. Although kidney function is almost normalized by KT, immunosuppressive therapy is essential to maintain kidney allograft function and to prevent rejection. However, these patients are more susceptible to infection due to the immunosuppressive therapy required to maintain kidney allograft function. Thus, both CKD and KT present disadvantages in terms of suppression of immune function. Periodontal disease is defined as a chronic infection and inflammation of oral and periodontal tissues. Periodontal disease is characterized by the destruction of connective tissues of the periodontium and alveolar bone, which may lead to not only local symptoms but also systemic diseases, such as cardiovascular diseases, diabetes, liver disease, chronic obstructive pulmonary disease, and several types of cancer. In addition, the prevalence and severity of periodontal disease are significantly associated with mortality. Many researchers pay special attention to the pathological roles and clinical impact of periodontal disease in patients with CKD or KT. In this review, we provide information regarding important modulators of periodontal disease to better understand the relationship between periodontal disease and CKD and/or KT. Furthermore; we evaluate the impact of periodontal disease on various pathological conditions in patients with CKD and KT. Moreover, pathogens of periodontal disease common to CKD and KT are also discussed. Finally, we examine the importance of periodontal care in these patients. Thus, this review provides a comprehensive overview of the pathological roles and clinical significance of periodontal disease in patients with CKD and KT.

C/EBPß and YY1 bind and interact with Smad3 to modulate lipopolysaccharide-induced amelotin gene transcription in mouse gingival epithelial cells.

Junctional epithelium (JE) develops from reduced enamel epithelium during tooth formation and is critical for the maintenance of healthy periodontal tissue through ensuring appropriate immune responses and the rapid turnover of gingival epithelial cells. We have previously shown a relationship between inflammatory cytokines and expression of JE-specific genes, such as amelotin (AMTN), in gingival epithelial cells. Here, we elucidated the effects of Porphyromonas gingivalis-derived lipopolysaccharide (Pg LPS) on Amtn gene transcription and the interaction of transcription factors. To determine the molecular basis of transcriptional regulation of the Amtn gene by Pg LPS, we performed real-time PCR and carried out luciferase assays using a mouse Amtn gene promoter linked to a luciferase reporter gene in mouse gingival epithelial GE1 cells. Gel mobility shift and chromatin immunoprecipitation assays were performed to identify response elements bound to LPS-induced transcription factors. Next, we analyzed protein levels of the LPS-induced transcription factors and the interaction of transcription factors by western blotting and immunoprecipitation. LPS increased Amtn mRNA levels and elevated luciferase activities of constructs containing regions between -116 and -238 of the mouse Amtn gene promoter. CCAAT/enhancer-binding protein (C/EBP) 1-, C/EBP2- and Ying Yang 1 (YY1)-nuclear protein complexes were increased by LPS treatment. Furthermore, we identified LPS-modulated interactions with C/EBPß, YY1 and Smad3. These results demonstrate that Pg LPS regulates Amtn gene transcription via binding of C/EBPß-Smad3 and YY1-Smad3 complexes to C/EBP1, C/EBP2 and YY1 response elements in the mouse Amtn gene promoter.

T cell and periosteum cooperation in osteoclastogenesis induced by lipopolysaccharide injection in transplanted mouse tibia.

BACKGROUND/PURPOSE: We previously reported that injedctions of lipopolysaccharide (LPS) into the gingiva of mice induce inflammatory bone resorption that actively involved T cells. Receptor activator of NF-κB ligand (RANKL), which is an essential factor for osteoclastogenesis, was reportedly produced by osteoblasts, fibroblasts, and T cells in vitro; however, it has not been established which cells affect osteoclastogenesis in vivo. Here we determined the roles of T cells and the periosteum on osteoclastogenesis in LPS-induced inflammatory bone resorption. MATERIALS AND METHODS: Thirty-five BALB/c (wild-type: WT) and 10 BALB/c-nu/nu (nude: Nu) mice congenitally lacking T cells were used. Using inbred WT mice, tibias were transplanted with and without the periostea [(+) and (-), respectively, n = 15 per group] into the dorsal subcutaneous connective tissue of WT or Nu mice. Each group received four injections around the transplanted site: experimental groups were injected with LPS, and control groups were injected with phosphate-buffered saline. Isolated tissues were prepared for histopathological observation of the transplanted bone surface. RESULTS: Many infiltrating inflammatory cells were present near the surface of the tibias in the LPS-injected groups. Only the WT (+) LPS group showed osteoclasts. The number of mononuclear preosteoclasts and RANKL-positive cells was highest in the WT (+) LPS group, and there were no significant differences among the other three groups. CONCLUSION: T cells and the periosteum are closely involved in osteoclastogenesis in inflammatory bone resorption in vivo.