Hypoxic dental pulp stem cells-released succinate promotes osteoclastogenesis and root resorption.

Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.

Influence of alveolar bone thickness and bucco-palatal inclination on root resorption of lateral incisors in unilateral maxillary impacted canines: a retrospective observational study.

BACKGROUND: This study aimed to investigate the potential associations between alveolar bone thickness, bucco-palatal inclination of maxillary lateral incisors, and lateral incisor root resorption in patients with unilateral maxillary impacted canines (UMICs). METHODS: A total of three hundred and five subjects (120 males, 185 females; mean age, 16.39 years; standard deviation, 4.04) with UMICs were included. Canine position and root resorption were assessed using CBCT. UMICs were divided into palatal, buccal and mid-alveolus groups (PICs, BICs and MAICs), with 117, 137 and 51 subjects, respectively. Alveolar bone thickness and bucco-palatal inclination of lateral incisors were measured using the Dolphin software. RESULTS: The prevalence of lateral incisor root resorption was significantly lower in the BICs (13.9%) than MAICs (29.4%) and PICs (29.1%). Alveolar bone thickness of the apical area was smaller in UMICs with lateral incisor root resorption than no resorption in both PICs (8.33 ± 1.64 vs 10.53 ± 2.55 mm) and BICs (8.94 ± 1.85 vs 10.76 ± 2.28 mm). Furthermore, lateral incisors on the impacted side were more buccally inclined in PICs with lateral incisor root resorption than no resorption, while in both BICs and MAICs, there was no statistical difference between lateral incisor root resorption than no resorption. Moreover, alveolar bone thickness of the apical area, rather than bucco-palatal inclination of lateral incisors, was significantly correlated with lateral incisor root resorption both in PICs and BICs. CONCLUSIONS: Lateral incisor root resorption is less common in BICs. Thinner alveolar bone thickness at the apical area of lateral incisors can be considered as a potential risk factor for lateral incisor root resorption in UMICs.

Uprighting horizontally impacted third molars by super-elastic nickel-titanium wire in patients with an extracted first molar.

Protracting lower second molars and uprighting horizontally impacted third molars is a significant orthodontic challenge in patients who require the extraction of severely decayed first molars. Here, we describe the use of biomechanics to upright 90°-tilted lower third molars following second molar protraction. Herein, we introduce a technique for uprighting the lower third molars by (1) the placement of superelastic nickel titanium archwires, (2) bonding, and (3) repositioning of a buccal tube in a tilted position to compensate for the efficiency of Ni-Ti (nickel-titanium) wire. The treatment mechanics used for our two cases showed that even severely impacted third molars can be uprighted by routine continuous straight-wire techniques. This technique proved to be a simple, efficient and reliable treatment option for uprighting horizontally impacted third molars.

Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens.

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF). Immunization with HPF resulted in increased PA0833-specific antibody titers, higher protective efficacy, and decreased bacterial burden and pro-inflammatory cytokine secretion compared with PA0833 immunization alone. Using fluorescently labeled antigens to track antigen uptake and delivery, we found that HlaH35A fusion significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that the increased antigen uptake after immunization with HPF was mainly due to monocyte- and macrophage-dependent macropinocytosis, which was probably the result of HPF binding to ADAM10, the Hla host receptor. Furthermore, a transcriptome analysis showed that several immune signaling pathways were activated by HPF, shedding light on the mechanism whereby HlaH35A fusion improves immunogenicity. Finally, the improvement in immunogenicity by HlaH35A fusion was also confirmed with two other antigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, indicating that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.

PINK1-mediated mitophagy reduced inflammatory responses to Porphyromonas gingivalis in macrophages.

OBJECTIVE: Mitochondria are strained by microbial stimuli in the periodontal niche. Damaged mitochondria are cleared by mitophagy. The purpose of the study was to explore whether mitophagy participated in the progress of periodontitis and whether activation of mitophagy can inhibit inflammatory responses to bacterial infection in macrophages. METHODS: Mitophagy-related genes were measured in the healthy and inflamed human gingiva. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis. Dexmedetomidine, urolithin A, and resveratrol were used to activate mitophagy, while small interference RNA was utilized to knock down PTEN-induced putative protein kinase 1 (PINK1). Activation of mitophagy-related genes and colocalization of them were detected by Western blot and confocal imaging. Damages of mitochondria, accumulation of mitochondrial reactive oxygen species (mtROS), and production of IL-1ß, IL-6, and TNF-α were measured. RESULTS: Levels of mitophagy-related genes were decreased in inflamed periodontal tissues and P. gingivalis-infected BMDMs. Dexmedetomidine, urolithin A, and resveratrol activated mitophagy, leading to reduced mitochondria damages, decreased mtROS generation, and inhibited IL-1ß, IL-6, and TNF-α production. PINK1 knockdown reduced dexmedetomidine, urolithin A, and resveratrol-induced anti-inflammatory effect. CONCLUSION: Inhibited mitophagy participated in the progress of periodontitis. Activation of mitophagy may become a therapeutic target during the progress of periodontitis by reducing mtROS.

Diagnostic accuracy of severe periodontitis for Ramfjord teeth based on different classifications.

OBJECTIVE: To evaluate the accuracy of Ramfjord teeth (RT) protocol for the diagnosis of severe periodontitis based on different classifications and explore the misclassification bias such as teeth loss. METHODS: Patients (n = 435) receiving full-mouth periodontal examination (FMPE) were included. Patients were classified as severe (stage III/IV) periodontitis and no/mild/moderate (no/stage I/II) periodontitis according to the case definition proposed by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP)-(CDC/AAP), a new classification introduced by AAP and the European Federation of Periodontology (EFP)-(AAP/EFP), and consensus of Chinese experts (CCE). Sensitivity, specificity, positive predictive value, negative predictive value, Youden's index, and area under the receiver operating characteristic curve (AUROC) compared with FMPE were evaluated. RESULTS: The specificity of RT was 86.8%, 92.2%, and 77.1% when compared with FMPE protocol based on CDC/AAP, AAP/EFP, and CCE classifications, while the AUROC value was 0.934, 0.961, and 0.886 specifically. The loss of the first molar leads to the greatest reduction in the detection rate of severe periodontitis. CONCLUSIONS: RT showed the highest specificity based on the new AAP/EFP classification. The loss of the first molar leads to the greatest reduction in the detection rate of severe periodontitis.

Hexokinase 2-mediated glycolysis supports inflammatory responses to Porphyromonas gingivalis in gingival fibroblasts.

BACKGROUND: When infected with Porphyromonas gingivalis, gingival fibroblasts undergo metabolic reprogramming, and rely on aerobic glycolysis rather than oxidative phosphorylation for rapid energy replenishment. Hexokinases (HKs) are catalysts for glucose metabolism, and HK2 constitutes the major HK inducible isoform. The objective of this study is to determine whether HK2-mediated glycolysis promotes inflammatory responses in inflamed gingiva. METHODS: Levels of glycolysis-related genes were assessed in normal and inflamed gingiva. Human gingival fibroblasts were harvested and infected with Porphyromonas gingivalis in order to mimic periodontal inflammation. 2-deoxy-d-glucose, an analogue of glucose, was used to block HK2-mediated glycolysis, while small interfering RNA was used to knock down HK2 expression. The mRNA and protein levels of genes were analyzed by real-time quantitative PCR and western blotting, respectively. HK2 activity and lactate production were assessed by ELISA. Cell proliferation was assessed by confocal microscopy. The generation of reactive oxygen species was assessed by flow cytometry. RESULTS: Elevated expression of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 was observed in the inflamed gingiva. P. gingivalis infection was shown to promote glycolysis in human gingival fibroblasts, as evidenced by increased gene transcription of HK2 and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3, cell glucose consumption, and HK2 activity. Inhibition and knockdown of HK2 resulted in reduced cytokine production, cell proliferation, and reactive oxygen species generation. Furthermore, P. gingivalis infection activated the hypoxia-inducible factor-1α signaling pathway, thus promoting HK2-mediated glycolysis and proinflammatory responses. CONCLUSIONS: HK2-mediated glycolysis promotes inflammatory responses in gingival tissues, and therefore glycolysis can be targeted in order to inhibit the progression of periodontal inflammation.

A novel periodontal endoscopy-aided non-incisional periodontal regeneration technique in the treatment of intrabony defects: a retrospective cohort study.

BACKGROUND: Gingival recession and post-operation discomfort are still a problem for patients receiving the periodontal regeneration surgery for intra-bony defects. To further reduce the trauma and the post-operation gingival recession, a novel periodontal endoscopy-aided non-incisional regeneration technique (NIT) was proposed in the treatment of intra-bony defects. METHODS: Retrospective analysis of 21 subjects treated with NIT and 21 subjects with periodontal endoscopy-aided scaling and root planing (PSRP) at baseline and 1-year evaluation was conducted. After removing the subgingival calculus and granulation tissue, bone grafting materials were placed into intrabony defects with the assistance of a gingival retractor in the NIT group. Probing depth (PD), gingival recession (GR), clinical attachment level (CAL), as well as the distance between bone crest (BC) level and base of the defect (BD) (intrabony defect depth, IBD) were evaluated at baseline and 1 year after treatment. RESULTS: At 1-year follow-up, the value of CAL, PD and IBD were statistically significant different compared with baseline in both two groups (p<0.001). CAL gain (p = 0.012) and PD reduction (p = 0.004) was greater in the NIT than PSRP. However, no difference in the IBD reduction was found between the NIT group and PSRP. Better CAL gain and PD reduction was achieved in the 1-year term in the NIT when compared with PSRP. CONCLUSION: NIT have resulted in significant gains in both clinical and radiographic parameters. NIT might be utilized as an alternative of the surgical treatment for periodontal intrabony defects. TRIAL REGISTRATION: This clinical trial registration was registered retrospectively (August 3, 2023) and the number is ChiCTR2300074317.

Self-reported oral health habits, knowledge and conditions of schoolchildren and adolescents in mainland China.

To determine the oral health habits, knowledge and conditions of students in China and investigate the impact of associated factors. A self-reported online questionnaire was distributed through social networks in mainland China to assess the oral health habits, knowledge, and conditions of students aged 6-20 years attending primary, middle, and high schools. Factors potentially associated with oral health, such as oral health habits of their parents, family education level, and economic regions, were analyzed using McNemar's and Chi-square tests. Within one month, 5561 valid questionnaires were retrieved from all 31 provinces or equivalent regions in mainland China. The results showed that 46.9% of students suffered from bleeding when brushing their teeth, while only 11.8% reported professional teeth cleaning at a dental clinic. Soda beverages were widely consumed among them (75.4%). A significant minority of students brushed their teeth less than twice daily (22.8%) and for about 2 minutes each time (19.3%). Only 21.9% of the students had preventive oral health care. Students' toothbrushing habits and knowledge about interdental cleaning tools were associated with parental habits (p < 0.001). Overall, students from families with higher educational backgrounds and eastern China had better oral health habits, knowledge, and conditions. There is a need to pay more attention to gingival health and caries prevention among schoolchildren and adolescents in mainland China. Improving parental oral hygiene habits could have a positive impact on the oral health of students. Further research on oral health among students is needed in the middle and western regions of China.

Nuclear receptor coactivator 4-mediated ferritinophagy drives proliferation of dental pulp stem cells in hypoxia.

Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy has been implicated in the ferroptosis in cancer cells and hematopoiesis in the bone marrow. However, the role of iron metabolism, especially NCOA4-mediated degradation of ferritin, has not been explored in the proliferation of mesenchymal stem cells. The present study was designed to explore the role of NCOA4-mediated ferritinophagy in hypoxia-treated dental pulp stem cells (DPSCs). Hypoxia treatment increased ROS generation, boosted cytosolic labile iron pool, increased expression of transferrin receptor 1 and NCOA4. Moreover, colocalization of LC3B with NCOA4 and ferritin was observed in hypoxia-treated DPSCs, indicating the development of ferritinophagy. Hypoxia promoted the proliferation of DPSCs, but not ferroptosis, under normal serum supplement and serum deprivation. NCOA4 knock-down reduced ferritin degradation and inhibited proliferation of DPSCs under hypoxia. Furthermore, the activation of hypoxia inducible factor 1α and p38 mitogen-activated protein kinase signaling pathway was involved in the upregulation of NCOA4 in hypoxia. Therefore, our present study suggested that NCOA4-mediated ferritinophagy promoted the level of labile iron pool, leading to enhanced iron availability and elevated cell proliferation of DPSCs. Our present study uncovered a physiological role of ferritinophagy in the proliferation and growth of mesenchymal stem cells under hypoxia.

NCOA4-mediated ferritinophagy promoted inflammatory responses in periodontitis.

BACKGROUND/OBJECTIVES: Iron homeostasis plays a crucial role in the combat against pathogen invasion. Ferrous iron can trigger generous production of reactive oxygen species (ROS) by Fenton reaction. Nuclear receptor coactivator 4 (NCOA4), a selective cargo receptor to deliver ferritin to lysosome, may trigger release of ferritin-bound iron into the cytosol. The aim of the present study was to explore whether NCOA4-mediated ferritinophagy participated in the pathogenesis of periodontitis, and its role in promoting the periodontal inflammation. METHODS: Inflamed and healthy periodontal tissues were harvested for immunobiological staining of ferritinophagy-related genes in the periodontal tissues, while real-time quantitative PCR (qPCR) was utilized to detect mRNA transcription. Periodontal ligament fibroblasts (PDLFs) were isolated and infected with Porphyromonas gingivalis. The mRNA transcription and protein expression of genes involved in the iron metabolism, including NCOA4, transferrin receptor 1 (TFR1), and ferroportin (SLC40A1) were detected by qPCR and western blot. Levels of labile iron pool and ROS production were detected by flow cytometry and confocal endoscopy. Small interference RNA was utilized to knock down NCOA4. RESULTS: Elevated expression of NCOA4, ferritin heavy chain, and light chain were observed in the diseased periodontal tissues. P. gingivalis infection promoted expression of TFR1, NCOA4, and microtubule-associated protein 1-light chain 3 B (LC3B), enhanced levels of intracellular labile iron pool and ROS production. NCOA4 knockdown reduced ROS generation in PDLFs in response to P. gingivalis and mitigated production of pro-inflammatory monocyte chemoattractant protein-1 and interleukin 6. P. gingivalis triggered activation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling pathway. In addition, inhibitors of JNK, SP600125, and inhibitors of p38, SB203580 blocked NCOA4 transcription. CONCLUSION: NCOA4-ferritinophagy participated in the progress of periodontitis progression. P. gingvalis-triggered ferritinophagy aggravated production of ROS and inflammatory responses in PDLFS. These findings suggest iron homeostasis plays an important role in the pathogenesis of periodontitis.

Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase-HIF-1α axis.

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH-HIF-1α axis may facilitate host modulation therapy of chronic periodontitis.

Torque expression by active and passive self-ligating brackets in patients with four premolar extractions: A retrospective study.

OBJECTIVE: Appropriate torque expression contributes to ideal treatment outcomes both clinically and aesthetically. Whether active and passive self-ligating brackets (SLBs) have different torque-control capability in vivo has never been reported. The purpose of present study was to explore whether there was difference in torque expression in active and passive SLBs. SETTING AND SAMPLE POPULATION: In this retrospective study, 225 patients with four first premolar extractions were enrolled. For each patient, the digital lateral cephalometric radiographs were taken before and after treatment. MATERIALS AND METHODS: The study consisted of 2 groups: 111 subjects were treated with passive SLBs (Damon Q, Ormco) and 114 subjects with active SLBs (Empower 2, American Orthodontics). Measurements to determine skeletal changes and incisor inclination were obtained from cephalometric tracings using Dolphin software (version 11.8, USA). Comparisons in both groups and intergroups were compared using t tests and chi-square test. RESULTS: Significant differences in the variation of U1-SN(°), U1-NA(°), L1-NB(°) and L1-FH(°) were found between two groups. More labially inclined maxillary incisors were found in active SLB group, while more labially inclined mandibular incisors were observed in passive SLB group. CONCLUSIONS: With the present prescription set in the two brackets, active SLBs achieved more proclined maxillary incisors and retroclined mandibular incisors. Clinicians should take torque expression of brackets into consideration during orthodontic treatment.

Treatment in a patient with congenital loss of both mandibular lateral incisors and severely retroclined maxillary central incisors.

This case report describes the treatment of a patient with congenital loss of both mandibular lateral incisors and severely retroclined maxillary incisors. The treatment included bilateral extraction of the maxillary first premolars, accurate 3-digital setup, a 2-stage torque control strategy, and intricate mechanic management. The dilemma of tooth-size discrepancy was solved by ideal torque control to avoid interproximal enamel reduction. An ideal Class I molar and canine relation, as well as canine guidance in the lateral excursion movement, was achieved with good stability.

A novel in situ bone elevation method to achieve vertical periodontal augmentation in dogs: A pilot study.

OBJECTIVES: The purpose of this study was to investigate whether a novel in situ interdental bone elevation method could achieve vertical bone augmentation around natural teeth. METHODS: Horizontal periodontal bone defects were created at nine quadrants of mandibles in five dogs. Six weeks later, one of the nine quadrants was randomly chosen as the model control. The remaining mandibles were allocated into two experimental groups: cortical bone removing (CBR) or interdental bone elevation (IBE). For the IBE group, four millimetres of interdental bone blocks were separated and elevated from the base of alveolar bone. Then bone xenografts were implanted beneath the elevated alveolar blocks. Animals were euthanised 12 weeks post-operation. Cone beam computed tomography (CBCT) examination and histological analysis were performed to evaluate the surgical outcomes. RESULTS: Enhanced soft tissue profiles were observed in the two experimental groups as compared to the model control group. CBCT images showed that the height of alveolar bone was significantly higher in the IBE group with bone blocks seated near the cementoenamel junction. Significantly larger area of bone tissues with the highest coronal level of new bone was observed in the IBE group. New bone was observed around the elevated bone blocks with bone remodelling and neovascularisation inside the elevated blocks. CONCLUSIONS: Vertical bone augmentation at interdental sites may be performed through in situ interdental bone elevation for patients with horizontal alveolar bone resorption.

The Suppressive Effects of the Petroleum Ether Fraction from Atractylodes lancea (Thunb.) DC. On a Collagen-Induced Arthritis Model.

In Chinese traditional medicine, the rhizome of Atractylodes lancea (Thunb.) DC. (A. lancea) is used extensively for the treatment of several diseases such as rheumatic diseases, but its actions on rheumatoid arthritis have not been clarified. The purpose of this article was to investigate the pharmacological effect of an A. lancea rhizome extract on collagen-induced arthritis (CIA) in rats. The CIA model was induced by the injection of bovine type II collagen. The rats were orally administered the petroleum ether (PE) fraction of the A. lancea rhizome (0.82 and 1.64 mg/kg), methotrexate (0.3 mg/kg body weight), or a vehicle from day 7 to day 15 after the model was established. The histological examination and radiological observation showed that the PE fraction significantly reduced the inflammatory responses and collagen loss in the joints of the rats with CIA. The PE fraction inhibited the production of tumor necrosis factor-α, interleukin (IL)-1ß, IL-17, and IL-6 in the sera. Moreover, the treatment with the PE fraction in vivo was able to reduce the level of Beclin 1 protein in the synovial tissue of the rats. These results highlight the antiarthritic potential of the PE fraction of the A. lancea rhizome and provide further evidence of the involvement of Beclin 1 inhibition in the effects of the PE fraction of the A. lancea rhizome. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of Intravenous Injection of Porphyromonas gingivalis on Rabbit Inflammatory Immune Response and Atherosclerosis.

The effects of intravenous injection of Porphyromonas gingivalis (Pg) on rabbit inflammatory immune response and atherosclerosis were evaluated by establishing a microamount Pg bacteremia model combined with high-fat diet. Twenty-four New Zealand rabbits were randomly divided into Groups A-D (n = 6). After 14 weeks, levels of inflammatory factors (C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)) in peripheral blood were detected by ELISA. The aorta was subjected to HE staining. Local aortic expressions of toll-like receptor-2 (TLR-2), TLR-4, TNF-α, CRP, IL-6, matrix metallopeptidase-9, and MCP-1 were detected by real-time PCR, and those of nuclear factor-κB (NF-κB) p65, phospho-p38 mitogen-activated protein kinase (MAPK), and phospho-c-Jun N-terminal kinase (JNK) proteins were detected by Western blot. Intravenous injection of Pg to the bloodstream alone induced atherosclerotic changes and significantly increased systemic and local aortic expressions of inflammatory factors, NF-κB p65, phospho-p38-MAPK, and JNK, especially in Group D. Injection of microamount Pg induced inflammatory immune response and accelerated atherosclerosis, in which the NF-κB p65, p38-MAPK, and JNK signaling pathways played important roles. Intravenous injection of Pg is not the same as Pg from human periodontitis entering the blood stream. Therefore, our results cannot be extrapolated to human periodontitis.

MAT2A inhibition suppresses inflammation in Porphyromonas gingivalis-infected human gingival fibroblasts.

Background: Methionine adenosyl transferase II alpha (MAT2A) is the key enzyme to transform methionine into S-adenosylmethionine (SAM), the main methylgroup donor involved in the methylation. The purpose of our study wasto explore whether MAT2A-mediated methionine metabolism affected theexpression of inflammatory cytokines in human gingival fibroblasts(hGFs). Methods: Both healthy and inflamed human gingiva were collected. HGFs werecultured and treated with P. gingivalis, with or without MAT2Ainhibitor (PF9366), small interference RNA (siRNA), or extrinsic SAMpretreatment. The levels of inflammatory cytokines were detected byreal-time PCR, western blotting, and ELISA. SAM levels were detectedby ELISA. The nuclear factor-kappa B (NF-κB) and mitogen-activatedprotein kinase (MAPK) pathway was explored by western blotting. Results: The expression of MAT2A was increased in the inflamed tissues. P.gingivalis infection promoted the expression of MAT2A and SAM inhGFs. Meanwhile, PF9366 and MAT2A-knockdown significantly decreasedexpression of inflammatory cytokines and SAM production. PF9366inhibited activation of NF-κB/MAPK pathway in P. gingivalis-treatedhGFs. Conclusions: MAT2A-mediated methionine metabolism promoted P. gingivalis-inducedinflammation in hGFs. Targeting MAT2A may provide a novel therapeuticmethod for modulating periodontitis.

Clinical and radiographic evaluation of Bio-Oss granules and Bio-Oss Collagen in the treatment of periodontal intrabony defects: a retrospective cohort study.

OBJECTIVE: This retrospective study aimed to analyze the clinical efficacy of two regenerative surgical methods - Bio-Oss granules combined with barrier membranes and Bio-Oss Collagen alone - and to help clinicians achieve better periodontal regeneration outcomes in the specific periodontal condition. METHODOLOGY: Patients who underwent periodontal regeneration surgery from January 2018 to April 2022 were retrospectively screened, and their clinical and radiographic outcomes at 6 months postoperatively were analyzed. The probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), gingival recession (GR), distance from the cemento-enamel junction to the bottom of the bone defect (CEJ-BD), and depth of intrabony defects (INFRA) were recorded before the operation (T0) and 6 months after it (T1), and subsequently compared. RESULTS: In total, 143 patients were included - 77 were placed in the Bio-Oss group and 66 were placed in the Bio-Oss Collagen group. All indicators, including PD and CAL at T1, showed significant differences compared to baseline, for both groups (P<0.001). PD reduction was greater in the group receiving the Bio-Oss Collagen treatment (P=0.042). Furthermore, in cases when the baseline PD range was 7-11 mm and the age range was 35-50 years, PD reduction was more significant for patients receiving the Bio-Oss Collagen treatment (P=0.031, 0.023). A linear regression analysis indicated that postoperative PD and CAL were positively correlated with baseline values, and that the efficacy tended to decrease with increasing age. CONCLUSION: Both the use of Bio-Oss Collagen alone and the use of Bio-Oss granules combined with barrier membranes resulted in significant effects in the treatment of periodontal intrabony defects. The Bio-Oss Collagen treatment generated more improvements in PD than the Bio-Oss granules combined with barrier membranes, particularly within the baseline PD range of 7-11 mm and the 35-50 years age group. Additionally, age was the main factor influencing the effectiveness of regenerative surgery for intrabony defects: older individuals exhibited fewer improvements.

Mitochondrial ROS participates in Porphyromonas gingivalis-induced pyroptosis in cementoblasts.

This study aimed to investigate correlation between mitochondrial reactive oxygen species and Porphyromonas gingivalis in the process of cementoblast pyroptosis. Lactate dehydrogenase activity assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry analysis were utilized to explore whether Porphyromonas gingivalis triggered pyroptosis in cementoblasts. Reactive oxygen species and mitochondrial reactive oxygen species were detected using flow cytometry and fluorescence staining. The effect of mitochondrial reactive oxygen species on the Porphyromonas gingivalis-induced pyroptosis of cementoblasts was assessed by Mito-Tempo, mitochondrion-targeted superoxide dismutase mimetic. Phosphorylation levels of p65 were measured by western blotting. SC75741, a nuclear factor-kappa B inhibitor, was added to block the nuclear factor-kappa B in the Porphyromonas gingivalis-infected cementoblasts. Porphyromonas gingivalis triggered pyroptosis of cementoblasts, and an elevation in reactive oxygen species generation in the mitochondria was observed. Inhibition of mitochondrial reactive oxygen species reduced pyroptosis and nuclear factor-kappa B signaling pathway mediated the pyroptotic cell death in Porphyromonas gingivalis-infected cementoblasts. Together, our findings demonstrate that mitochondrial reactive oxygen species increased by Porphyromonas gingivalis participated in the pyroptosis of cementoblasts. Targeting mitochondrial reactive oxygen species may offer therapeutic strategies for root surface remodeling or periodontal regeneration.