International Journal of Oral Science
·
2026
·Vol. 18
·期 1
·6
·
IF 17.6
Guo Jiajie,Qiu Qiujing,Yan Xiaoyuan,Zhang Zeying,Zhang Xiyue,An Na,Yin Chengcheng,Yang Di,Okamura Hirohiko,Yoshida Kaya,Sun Hongchen,Qiu Lihong
Rheumatoid arthritis (RA) is an autoimmune disorder that triggers progressive joint destruction by inducing excessive osteoclastogenesis. Porphyromonas gingivalis ( Pg ), the main pathogenic bacterium involved in periodontitis (PD), is closely related to RA. Pg can secrete extracellular vesicles (EVs), which carry numerous virulence factors. The aim of this study was to investigate whether Pg- derived EVs can be transported and exacerbate bone destruction in RA by promoting osteoclastogenesis and to elucidate the underlying mechanisms involved. EVs derived from Porphyromonas endodontalis ( Pe ), which is weakly associated with PD or RA, were used as controls. Pg and Pe EVs interact with osteoclasts after translocating into the marrow and metacarpal joints of mice. In vitro, Pg EVs induce osteoclastogenesis via various components, such as lipopolysaccharide, proteins, lipoproteins, and proteases. TNF-α, IL-1β, and IL-6 promote but cannot independently control Pg EV-induced osteoclastogenesis. RNA sequencing and verification experiments further demonstrated that Pg EVs induced osteoclastogenesis by promoting the phosphorylation of spleen tyrosine kinase (Syk). In vivo, Pg EVs exacerbated RA-induced bone destruction by activating Syk-dependent osteoclastogenesis. R406, a Syk inhibitor, significantly attenuated Pg EV-induced RA osteoclastogenesis and bone destruction. However, Pe- derived EVs presented an extremely weak ability to promote osteoclastogenesis and RA. Our findings reveal a new mechanism by which Pg EVs can exacerbate RA via transport through the circulation and the promote Syk-dependent osteoclastogenesis. This study deepens our understanding of the significant pathogenic role of EVs derived from oral bacterial in RA and explores targeted therapeutic strategies by inhibiting the activation of Syk.
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Frontiers in Microbiology
·
2025
·
IF 4.5
Yuqi Wang,Jun Ma,Haoyu Wang,Jingzheng Yi,Yuxin Bai,Min Hu,Jiaqing Yan
Introduction: Periodontitis and inflammatory bowel disease are chronic inflammatory diseases with shared epidemiological, biological, and therapeutic associations. Given the similarities in their pathogenic factors, this study hypothesized that mesalazine, a key treatment agent for inflammatory bowel disease, could also be effective in managing periodontitis.Methods: The antimicrobial effect of mesalazine on Porphyromonas gingivalis was investigated in vitro, including observations of morphological changes on the surface of P. gingivalis. Additionally, the impact of mesalazine on both the formation and established plaque biofilms was examined. The antimicrobial mechanism was elucidated by assessing the expression of P. gingivalis virulence genes and by determining the disruptive effect on P. gingivalis cell membranes. An in vivo rat model of periodontitis was constructed to evaluate mesalazine’s efficacy and its influence on the periodontal bacterial flora in the context of periodontitis.Results and discussion: Our results demonstrated that mesalazine concentrations ranging from 0.5 to 2 mg/mL significantly inhibited P. gingivalis proliferation over 72 h. Flow cytometry revealed a marked reduction in the number of viable cells following mesalazine treatment. At the nanometer scale, mesalazine induced crumpling and rupture of the P. gingivalis surface, compromising cell membrane integrity. Mesalazine not only suppressed the formation of plaque biofilms by P. gingivalis and polymicrobial communities but also disrupted pre-existing biofilms. The data also suggested that mesalazine could disrupt the integrity of the P. gingivalis cell membrane and inhibit the expression of virulence factors. An animal model of periodontitis in rats was successfully constructed in vivo. Mesalazine treatment inhibited alveolar bone resorption, alleviated inflammation of periodontal tissues, and improved the composition of the periodontal flora to a healthier state. This study establishes that mesalazine can treat periodontitis through modulation of the periodontal flora and its anti-inflammatory properties, thus broadening its classical therapeutic applications.
研究领域:
牙科
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微生物学
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药理学
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感染病学
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Journal of Dental Sciences
·
2024
·
IF 3.4
Xin-Yi Cheng,Pei-Hui Zou,Yi-Ming Ma,Yu Cai,Qiao Shi,Jia Liu,Qing-Xian Luan
Background/purpose Periodontitis is associated with systemic health. One of the underlying mechanisms is the translocation of periodontal pathogens, among which Porphyromonas gingivalis ( Pg ) is the most common. Here, we aimed to illustrate the biodistribution and dynamics of Pg from gingiva to multiple organs through blood circulation. Materials and methods Pg tagged by Cyanine 7 (Cy7- Pg ) was injected into the gingiva of healthy and periodontitis mice. In vivo imaging system (IVIS) was applied to monitor the distribution of Cy7- Pg in multiple organs which were isolated at serial timepoints. Polymerase chain reaction (PCR) was conducted to determine the Pg DNA copies in the gingiva, blood and organs. Cy7- Pg in the gingiva and organs was also confirmed by frozen section staining. Furthermore, to figure out whether the bacteremia derived from oral-gut axis, mice received gavage of Cy7- Pg . Then the blood and organ samples were detected in the similar way as above. Results Intra-gingival injection induced larger amounts of Cy7- Pg accumulating in the gingiva of periodontitis mice ( P < 0.05) as confirmed by above three methods. Twenty minutes after injection, Pg DNA copies in the blood of periodontitis group were 36.3-fold higher than healthy group ( P < 0.05). IVIS results, combined with PCR and frozen sections, demonstrated periodontitis induced longer retention with higher amounts of Cy7- Pg in the periodontitis group. Pg was enriched more significantly in the liver for the longer duration than the kidney and pancreas. Conclusion Our study showed Pg , which accumulated in the gingiva, could translocate through blood circulation to multiple organs with varied duration and amounts.
研究领域:
口腔医学
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感染性疾病
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分子影像学
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IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL
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2015
·Vol. 52
·期 2
·228-234
·
IF 1.145
Gao Aichao,Wang Xichao,Yu Haiyan,Li Na,Hou Yubo,Yu Weixian
Porphyromonas gingivali s ( Pg ) as the major pathogenic bacterium of chronic periodontitis can cause alveolar bone resorption. Lipopolysaccharide (LPS) is its main virulence factor. The Eph family plays an important role in maintaining bone homeostasis. In this study, the effects of P. gingivalis lipopolysaccharide ( Pg -LPS) on the expression of EphA2 in osteoblasts and osteoclasts were investigated. MC3T3-E1 cells and RAW264.7 cells were separately cultured in osteoblast-conditioned medium and osteoclast-conditioned medium to induce their differentiation into osteoblasts and osteoclasts, respectively. MC3T3-E1 cells were treated with 1 μg/mL of Pg -LPS 3, 7, and 14 d later, while RAW264.7 cells were treated with 10 μg/mL of Pg -LPS 1, 3, and 5 d later. The results have shown that Pg -LPS increased the expression of EphA2 both in osteoblasts and osteoclasts, decreased the expression of osteogenic-related genes ( ALP , Sp7 ), and increased the expression of osteoclast-related genes ( MMP9 , c-fos , ACP5 , CtsK , and NFATc1 ). Tartrate-resistant acid phosphatase (TRAP) staining illustrated that Pg -LPS promoted osteoclast differentiation and decreased the activity of alkaline phosphatase. Therefore, analysis indicates that, when treated with Pg -LPS, the expression of EphA2 is upregulated while the activity of osteoblasts and osteoclasts was reduced and increased, respectively. Our data suggest that EphA2 is closely related to the formation of osteoblasts and resorption of osteoclast and is likely to play an role in bone resorption induced in chronic periodontitis. These findings may provide information on new targets for prevention and treatment of chronic periodontitis.
研究领域:
牙医学
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免疫学
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分子生物学
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CELLULAR SIGNALLING
·
2025
·
IF 3.7
Yi-Jun Qi,Ye-Lin Jiao,Pan Chen,Qiao-Qing Zhu,Ran Guo,Dang-Rou Wu,Yu-Bo Du,Wan-Ying Li,Yue-Yue Cheng,Xiao-Shuang Wu,Meng-Xiang Li,Wei Li,Shegan Gao
Porphyromonas gingivalis ( P. gingivalis ), a keystone pathogen in adult periodontitis, is linked to an increased risk of many cancers. Although autophagy stimulated by P. gingivalis in ESCC has been reported, the molecular mechanisms and functional roles of autophagy in P. gingivalis -related ESCC progression are still unclear. P. gingivalis infection promoted the malignant progression of ESCC through autophagy, as demonstrated in both in vitro and in vivo studies. Once P. gingivalis invaded cancer cells, it induced the dephosphorylation and nuclear accumulation of YAP/TAZ, which are the effectors of Hippo pathway. In a TEAD-dependent manner, YAP/TAZ activated the miR-21-5p/RASA1/ERK signaling pathway to enhance autophagy-mediated tumor-promoting roles in the proliferation, migration, and invasion of ESCC. Additionally, P. gingivalis infection was correlated with higher levels of miR-21-5p, YAP/TAZ, and LC3, all of which were associated with shorter overall survival of patients with ESCC. Taken together, our findings reveal that the YAP/TAZ-miR-21-5p-ERK axis plays a crucial role in the P. gingivalis -infected subtype of ESCC, suggesting P. gingivalis and the autophagy pathway as promising therapeutic targets for ESCC treatment.
研究领域:
肿瘤学
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微生物学
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分子生物学
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口腔医学
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病理学
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MICROCHEMICAL JOURNAL
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2024
·
IF 4.9
Xuan Wu,Ning-Ning Pi,Fei Deng,Shi-Yang Tang,Cheng-Chen Zhang,Lu Zhu,Fang-Fang Sun,Xiao-Yao He,Han-Qing Li,Shi-Long Zhao,Rong Xiang,Yi Li
Periodontitis not only leads to tooth loss but is also associated with various systemic symptoms. Porphyromonas gingivalis ( Pg ) is the microorganism most closely linked to periodontitis. A rapid and accurate Pg detection method holds significant potential health benefits for patients. While several nucleic acid amplification-based diagnostic methods have been developed, there is a current lack of rapid diagnostic tools for Pg , particularly at chair-side level. Here, two detection methods for the Pg 16S gene based on the CRISPR/Cas12a system have been developed. To achieve ultra-high sensitivity in the developed CRISPR/Cas12a assays without pre-amplification, we designed a circular DNA molecule (termed as Cir-amplifier) which amplifies the signal output of the Cas12a reactions in a cascade response manner. The Cir-amplifier enhanced Fluorescence-Cas12a reaction achieved a minimum detectable limit of 0.39 CFU of Pg within 80-minute under room-temperature. In addition, the Cir-amplifier enhanced Lateral Flow Detection (LFD)-Cas12a reaction has demonstrated the ability to detect a minimum of 3.9 CFU of Pg in 90 min, with results observable by the naked eye. The potential of the two methods for Pg detection in clinical samples has been demonstrated, showing 100 % sensitivity compared to the traditional real-time PCR method. In summary, we have established two efficient detection methods for Pg that eliminate the need for pre-amplification, hence no amplicon contaminations, making them promising candidates for chair-side Pg diagnosis. Furthermore, the Cir-amplifier has been demonstrated to be adaptable to CRISPR/Cas systems producing various signal formats. The Cir-amplifier is expected to become a universal CRISPR/Cas enhancer.
研究领域:
分子生物学
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微生物学
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诊断学
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生物技术
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JOURNAL OF NANOBIOTECHNOLOGY
·
2025
·Vol. 23
·期 1
·1-24
·
IF 12.6
Qiu Qiujing,Yan Xiaoyuan,Zhang Zeying,Zhang Xiyue,Ma Jiawei,Gao Wenqing,An Na,Qiu Lihong,Guo Jiajie
Background Recent studies have implicated periodontitis (PD) as a potential risk factor for osteoporosis; however, the precise mechanisms remain unclear. Porphyromonas gingivalis ( Pg ), a key pathogen associated with PD, can secrete extracellular vesicles (EVs). However, whether Pg EVs can be transported to the bone marrow and influence osteoporosis-related osteoblast differentiation warrants exploration. This study compares Pg EVs with EVs from Porphyromonas endodontalis ( Pe ), which is a less virulent congener but the evidence for its pathogenicity in PD is weak. Results Pg EVs can be translocated into the marrow of mice and be internalized by osteoblasts through clathrin- and lipid raft-mediated endocytosis, thereby exacerbating osteoporosis. Pg EVs promote mitochondrial fission and inhibit mitochondrial fusion, leading to mitochondrial fragmentation, impaired mitochondrial activity and suppressed osteogenic differentiation. Furthermore, Pg EVs downregulate the protein level of carnitine palmitoyl transferase 2 (Cpt2) and inhibit fatty acid oxidation (FAO) by disrupting mitochondrial dynamics, which impairs osteoblast ATP production and exacerbates osteoporosis. The effects of Pe EVs are similar but weaker than those of Pg EVs. Conclusions This study elucidates that Pg EVs exacerbate osteoporosis by disrupting osteoblast mitochondrial dynamics and suppressing Cpt2-regulated FAO. This study contributes to understanding of the etiological mechanisms through which Pg contributes to the progression of osteoporosis and highlights the pivotal role of EVs in the association between periodontal disease and systemic diseases. Graphical
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SENSORS AND ACTUATORS B-CHEMICAL
·
2025
·
IF 7.7
Xiaolong Guo,Yan Zhao,Xuemei Xu,Zhibin Wu,Li Xiao,Xiaoyang Ma,Ziqiu Lei,Yilin Zhao,Chengli Zhang,Lixing Song,Minggang Yin
Rapid and accurate detection of Porphyromonas gingivalis ( P. gingivalis ) is crucial for the timely diagnosis and management of periodontal diseases as well as for elucidating its role in systemic conditions. However, conventional diagnostic methods are complex, time-consuming, and unsuitable for point-of-care testing, necessitating the development of a more efficient and accessible detection system. This study presents a novel dual-probe fluorescence platform featuring cadmium telluride quantum dots (CdTe QDs) and a specially designed probe (PAN) as fluorescent molecules, which does not require a washing step. The PAN and CdTe QD probes can efficiently differentiate between Cu 2 + and Cu + ions through ionic hydrolysis and cation exchange reactions, respectively, resulting in the sensitive and rapid detection of arginine-specific gingipain, a key biomarker for P. gingivalis . Furthermore, the color change of CdTe QDs upon contact with saliva samples facilitates the visual identification of P. gingivalis . This dual-probe platform demonstrated a higher signal-to-noise ratio and greater reliability compared to the single-probe methods. Moreover, this platform features a low detection limit of 5 and 20 colony-forming units (CFUs)/mL for the PAN and CdTe QDs signals, respectively, with a visual detection threshold as low as 200 CFU/mL. Thus, this platform provides quantitative and qualitative results that are 100 % in concordance with quantitative PCR results from clinical saliva samples of patients with periodontitis and healthy controls. This simple, rapid, and cost-effective diagnostic tool can be potentially used for point-of-care applications, enabling early detection and improved monitoring of oral health and related diseases.
研究领域:
生物医学工程
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微生物学
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牙科医学
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生物传感器
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纳米技术
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诊断检测
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ming Li,Ru Qu,Ping Li,Xuan Mo,Juan Liu,Biao Dong,Liting Liu,Zhenjiang Zech Xu
This study aimed to investigate the potential alleviating effect of Epimedium polysaccharide (EP) on intestinal inflammation aggravated by Porphyromonas gingivalis (Pg). P. gingivalis , an oral pathogen, may play a role in intestinal inflammation, highlighting the necessity to explore substances capable of inhibiting its pathogenicity. Initially, in vitro screening experiments utilizing co -culturing and quantitative polymerase chain reaction revealed that EP significantly inhibited the growth of P. gingivalis and the levels of virulence genes, including Kgp and RgpA. Subsequent mouse experiments demonstrated that EP notably ameliorated Pg-aggravated weight loss, disease activity index, histopathological lesions, and disruption of intestinal barrier integrity, evidenced by a reduction in tight junction protein levels. Flow cytometry analysis further illustrated that EP attenuated Pg-induced Th17 differentiation and Th17-related cytokines, such as IL-17 and IL-6. Additionally, 16S rRNA amplicon sequencing analysis elucidated that EP significantly mitigated Pg-induced gut microbiota dysbiosis, enriching potentially beneficial microbes, including Akkermansia and Bifidobacterium . The metabolomic analysis provided further insight, indicating that EP intervention altered the accumulation of relevant intestinal metabolites and exhibited correlations with disease indicators. In conclusion, our research suggested that EP holds promise as a prospective therapeutic agent for alleviating P. gingivalis -aggravated intestinal inflammation.
研究领域:
免疫学
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微生物学
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药理学
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胃肠病学
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BIOSENSORS & BIOELECTRONICS
·
2026
·
IF 11.8
Shaoqiong Feng,Keye Gong,Jincheng Xu,Pui Wing Yap,Tian Deng,Quanying Fu,Jianhua Zhou
Periodontitis, a highly prevalent chronic inflammatory disease, necessitates efficient screening methods. Detection of Porphyromonas gingivalis ( P. gingivalis ), a key periodontal pathogen, in saliva offers a promising non-invasive approach through the traditional methods such as bacterial culture and qRT-PCR for screening periodontitis. However, these traditional methods for detecting P. gingivalis are impractical for on-site and large-scale screening. To address these issues, this study developed a unidirectional-flow assay based on the surface microchannel (SMC) membrane. First, by targeting high-abundance rRNA, this assay eliminates the need for nucleic acid amplification. Second, by replacing commercial nitrocellulose membrane with SMC membrane, this assay effectively prevents the interception of probe/target nucleic acid complex during lateral flowing. This design significantly enhances the capture efficiency at the test line and the detection sensitivity. The experiment results demonstrated that this test strip achieved a limit of detection as low as 1.0×10 3 CFU/mL for P. gingivalis within 6 min and exhibited good specificity. Besides, the clinical experiments suggested that the results obtained by this assay were highly consistent with those from qRT-PCR and clinician diagnosis, further verifying its feasibility and potential for the rapid screening of periodontitis. This assay eliminates the need for nucleic acid amplification while maintaining high sensitivity, offering rapid and user-friendly operation for on-site and large-scale screening of periodontitis.
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RSC Advances
·
2020
·Vol. 10
·期 14
·8198-8206
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IF 3.119
Li-na Xu,Xiao-yu Yu,Wan-qing Chen,Song-mei Zhang,Jing Qiu
Objective: The study aims to investigate the biocorrosion behavior of Porphyromonas gingivalis on pure and SLA titanium surfaces and its effects on surface characteristics and osteoblast behavior. Methods: Pure and SLA titanium specimens were immersed in culture medium with P. gingivalis and incubated for 7 days. P. gingivalis colonization on the pure and SLA titanium surfaces was observed by scanning electron microscopy (SEM). The pure and SLA titanium surface characteristics were analyzed via X-ray photoelectron spectroscopy (XPS), surface roughness and surface wettability. The corrosion behaviors of pure and SLA titanium specimens were evaluated by electrochemical corrosion test. The osteoblast behavior of MC3T3-E1 cells on the pure and SLA titanium surfaces after P. gingivalis colonization was investigated by cell adhesion and western blot assays. Results: P. gingivalis colonized on the pure and SLA titanium surfaces was observed by SEM. The XPS analysis demonstrated reductions in the relative levels of titanium and oxygen and obvious reductions of dominant titanium dioxide (TiO2) on both titanium surfaces after immersing the metal in P. gingivalis culture. In addition, their roughness and wettability were changed. Correspondingly, the electrochemical corrosion test results revealed significant decreases in the corrosion resistance and increases in the corrosion rate of the pure and SLA titanium specimens after immersion in P. gingivalis culture. The results of the in vitro study showed that the pre-corroded pure and SLA titanium surfaces by P. gingivalis exhibited lower osteocompatibility and down-regulated the adhesion, spreading and osteogenic differentiation abilities of MC3T3-E1 cells. Conclusions: P. gingivalis was able to colonize on the pure and SLA titanium surfaces and weaken their surface properties, especially a decrease in the protective TiO2 film, which induced the biocorrosion and further negatively affected the osteoblast behavior.
研究领域:
材料科学
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生物学
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牙科材料
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细胞生物学
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Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 22
·4293-4305
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IF 7.571
Ning Gan,Wei Qin,Chunlei Zhang,Ting Jiao
Postoperative infection and poor osteogenesis will cause the failure of dental implant surgery. Thus, the antibacterial and osteogenic activities are the core requirements for the surface modification of dental implants. Inspired by the strong chelating ability of naturally occurring phytic acid (PA), an in situ deposition method on the surface of titanium implants was developed based on the metal–phosphate coordination networks. Biologically relevant metal cations (i.e. ferric ions and divalent copper ions) were selected as metal constituents for the construction of organic–inorganic coordination network films. The stability of PA–metal coordination bonds is rationally explained by the chemical nature of transition metal elements. This PA–metal coordination complex coating exhibited an excellent antibacterial activity against Porphyromonas gingivalis, reducing the bacterial implant colonization by > 3.92 log10. The abundant phosphate groups greatly increased the surface hydrophilicity, promoted the early adhesion of proteins, improved the proliferation of bone marrow mesenchymal stem cells, and finally achieved an enhanced osteogenic activity. In addition, the phosphate groups of PA also facilitated the deposition of hydroxyapatite by providing reaction sites to chelate with calcium ions. These findings evaluate the anti-bacterial and osteogenic potentials of PA–metal coordination complexes, and clarify the feasibility for surface modification of dental implants.
研究领域:
牙科材料
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生物材料
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表面化学
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生物医学工程
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微生物学
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组织工程
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高影响因子
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