Molecular Oral Microbiology最新文献

{"title":"Biosynthetic Gene Cluster Muf in Streptococcus mutans Predicts Longitudinal Caries Progression in Young Children.","authors":"Xinyue Li, Qiuping Chen, Runzhe Chen, Liang Zhang, Mianjia Wan, Jian Ma, Weiping Zhou, Yulin Yang, Hua Deng, Qun Huang","doi":"10.1111/omi.70042","DOIUrl":"https://doi.org/10.1111/omi.70042","url":null,"abstract":"<p><strong>Background: </strong>Streptococcus mutans (S. mutans) is a primary etiological agent in dental caries. However, longitudinal evidence regarding its role in caries initiation and progression remains limited. This study aimed to evaluate the utility of the muf biosynthetic gene cluster (BGC) in S. mutans as a predictor of caries occurrence and progression.</p><p><strong>Methods: </strong>We first conducted a case-control study to assess the prevalence of the muf BGC using quantitative polymerase chain reaction (qPCR). Subsequently, a prospective cohort study was performed to evaluate the cariogenic potential of muf. Caries increment over the follow-up period was compared between children harboring muf-positive and muf-negative S. mutans.</p><p><strong>Results: </strong>Initial screening targeting the glucosyltransferase B (gtfB) gene confirmed the presence of S. mutans. Among the 46 S. mutans-positive specimens, the prevalence of the muf locus was higher in children with caries (44.12%, 15/34) than in caries-free controls (16.67%, 2/12), corresponding to an odds ratio (OR) of 3.95. In the prospective cohort of 119 children, univariate analysis revealed that muf-positivity was associated with a 2.13-fold increased risk of caries increment over the 6-month follow-up (60.7% vs. 28.6%, p < 0.01). Importantly, this association remained robust after multivariable adjustment for potential confounders, with muf-positivity continuing to confer nearly twice the risk of developing new carious lesions (p < 0.01). Furthermore, an integrated risk stratification framework identified the double-positive (muf⁺/gtfB⁺) genotype as a high-risk factor for caries progression, yielding an RR of 6.21 compared to the muf^-/gtfB^- baseline.</p><p><strong>Conclusions: </strong>BGC muf-positive S. mutans is associated with increased caries progression in early childhood, highlighting its potential as a biomarker for identifying high-risk individuals.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149182976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pneumococcal-Driven Genetic Competence: A Key Driver of Pathobiont Adaptation and Disease Potential.","authors":"Indu Singh, Haritima Singh, Anushri Keshri, Priyanshi Sharma, Divakar Sharma, Arun Kumar, Megh Singh Dhakad, Mirza Masroor Ali Beg","doi":"10.1111/omi.70041","DOIUrl":"https://doi.org/10.1111/omi.70041","url":null,"abstract":"<p><p>High genetic variability in streptococci is driven by natural competence, specifically in Streptococcus pneumoniae and its close commensal species (Streptococcus pseudopneumoniae, Streptococcus oralis, and Streptococcus mitis), which drives rapid Streptococcal evolution. The genome of S. pneumoniae and its close commensal species exhibits high interspecies recombination, an open-pan genome, and a similar evolutionary origin. Mechanisms of natural competence are a highly regulated process driven by numerous molecular players at different stages. Natural competence in Streptococci drives the shift from commensal to pathogenic state. Streptococcus pneumoniae acquires various virulence and antibiotic-resistant genes (ARGs) via natural competence and also facilitates immune evasion, the emergence of multidrug-resistant strains, and capsule switching between strains. Most reports indicated that the natural competence in S. pneumoniae is a one-way street process; however, a few studies have proved that it is a two-way street process. The purpose of the current review is to elucidate (i) the genome of S. pneumoniae and its close relatives, (ii) the mechanism of HGT, (iii) HGT in S. pneumoniae and related commensal species, (iv) acquisition of drug-resistance genes and virulence factors, and (v) the implication of HGT in competence-driven gene transfer in IPD and interaction between host and pathogens.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hu Mei Qing Yan Ke Li Alleviates Periodontitis by Modulating the Oral Microbiome.","authors":"Xia Wang, Heqiong Zheng, Yunzhi Feng, Fengyi Zhang","doi":"10.1111/omi.70040","DOIUrl":"https://doi.org/10.1111/omi.70040","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a prevalent chronic inflammatory disease driven by dysbiosis of the oral microbiota. Hu Mei Qing Yan Ke Li (HM), a modern herbal formulation derived from Reynoutria japonica Houtt and Prunus mume Siebold & Zucc, exhibits anti-inflammatory, antioxidant, and antibacterial properties, suggesting promising therapeutic potential for periodontitis therapy. This study aimed to investigate the protective effects of HM against experimental periodontitis and further explore its underlying mechanisms.</p><p><strong>Methods: </strong>Periodontitis was induced by ligature placement in C57BL/6 mice. Mice were randomly assigned to the untreated periodontitis (P) and HM-treated (P + HM) groups. Mice in the P + HM group received HM via daily oral gavage at 6.58 mg/g body weight for 2 weeks. Alveolar bone loss was assessed by micro-CT analysis. Periodontal tissue destruction and osteoclast activity were evaluated by H&E, Masson's, and TRAP staining. Expression of OPG and RANKL was detected by immunofluorescence. Subgingival microbiota composition was analyzed by 16S rRNA sequencing.</p><p><strong>Results: </strong>HM treatment significantly inhibited osteoclastogenesis and alleviated alveolar bone resorption, while preserving periodontal tissue integrity. Quantitatively, HM treatment significantly increased BV/TV from 41.89% to 54.41% (p = 0.0019), Tb.Th from 111.5 to 131.2 µm (p = 0.0028), and Tb.Sp from 119.2 to 153.6 µm (p = 0.0015), while decreasing BS/BV from 0.03166 to 0.02655 1/µm (p = 0.0004). Mechanistically, HM upregulated OPG and downregulated RANKL expression in periodontal tissues. Notably, HM restructured the subgingival microbial community, suppressing the pathobiont Streptococcus acidominimus (16.95%-9.37%, p = 0.0411) and Rodentibacter_A_734545pneumotropicus (70.32%-16.46%, p < 0.0001), while enriching a beneficial consortium including Streptococcus danieliae (0.75%-30.68%, p < 0.0001), unclassified Corynebacterium (0.00%-6.50%, p = 0.0022), and unclassified Ligilactobacillus (1.57%-22.74%, p = 0.0063).</p><p><strong>Conclusion: </strong>HM alleviates periodontitis by remodeling the dysbiotic oral microbiome toward homeostasis and favorably modulating the OPG/RANKL axis in a murine ligature-induced periodontitis model.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Host-Microbe Mechanisms of Fusobacterium nucleatum in Colorectal Cancer.","authors":"Hadda Lyzandra Austríaco Leite, Fernanda Ferreira Lopes","doi":"10.1111/omi.70038","DOIUrl":"10.1111/omi.70038","url":null,"abstract":"<p><p>The oral-derived pathobiont Fusobacterium nucleatum has increasingly been implicated in colorectal cancer (CRC) progression through its ability to modulate inflammatory, immunological, and molecular pathways. F. nucleatum has emerged as a key oral-derived pathobiont frequently associated with tumor aggressiveness and alterations in the colorectal tumor microenvironment. This review critically examines recent mechanistic evidence from in vitro, in vivo, and advanced experimental models to elucidate how F. nucleatum interacts with host pathways involved in colorectal carcinogenesis. Available evidence indicates that this bacterium actively reshapes the tumor microenvironment through coordinated effects on immune signaling, epigenetic regulation, metabolic adaptation, and metastatic competence. Mechanistically, F. nucleatum promotes sustained inflammatory activation, macrophage polarization, epithelial-mesenchymal transition, endothelial remodeling, and resistance to regulated cell death pathways, while also influencing transcriptional and oncogenic programs associated with tumor progression. Emerging evidence further suggests that microbial effects may be modulated by tumor heterogeneity and long-term environmental exposures, reinforcing the complexity of host-microbiome interactions in CRC. Collectively, the findings support the concept that F. nucleatum functions as an active biological driver rather than a passive microbial bystander in CRC progression. These insights highlight the translational relevance of tumor-associated microbiota and support the need for approaches combining mechanistic, microbial, and clinical data to refine precision strategies at the tumor-microbiome interface.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"258-265"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of the Health-Associated Oral Microbiome in Young Nonhuman Primates.","authors":"J L Ebersole, O A Gonzalez","doi":"10.1111/omi.70033","DOIUrl":"10.1111/omi.70033","url":null,"abstract":"<p><p>Nonhuman primates have been shown to develop periodontitis with clinical and demographic features similar to humans. This preclinical disease model is well-positioned to advance the elucidation of novel biologic-based preventive and therapeutic approaches to controlling periodontitis, a chronic infection and immunoinflammatory disease. In this analysis, the oral microbiomes of younger (10-19 human years; n = 30) nonhuman primates are compared for matriline (an indicator of heritability), sex, and age variations. A holistic assessment of the microbiome similarities/differences suggested two primary conclusions in this younger group of orally healthy nonhuman primates. First, at the microbiome level of phyla, orders, and families, the ecology was relatively similar across sexes, matrilines, and age groups. However, at the genus level, matriline, sex, or age differences were observed. Of interest was that the principal differential genus proportions with matriline and age were similar, but somewhat unique with the sex comparison. These genus differences encompassed microorganisms generally considered as human commensals, albeit Fusobacterium, Tannerella, and Treponema genera did show some variation. The second, broader observation was the rather extensive species variation across these nonhuman primates. Nevertheless, the data could define a \"core microbial species\" pattern that included species across the Actinobiota, Bacteroidota, Desulfobacterota, Firmicutes/Bacillota, Fusobacteriota, Proteobacteriota, and Spirochaetota phyla. The results provide seminal details of the oral microbiome in this disease model and underpin the ability to elucidate specific microbial changes that can occur related to early-life oral environmental stimuli that may presage a greater risk for periodontitis in adulthood.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"266-279"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147960040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Regulation of Virulence and Dental Biofilm Formation in Streptococcus mutans: Unravelling the Crosstalk Between the VicRK and LiaSR Two-Component Systems.","authors":"Niher Tabassum Snigdha, Ruaa Abdullah Alamoudi, Nuha Saad Alghamdi, Mohammed Abdul Kader, Syed Nahid Basheer, Mushir Mulla, Munaz Mulla, Ankita Mathur, Mohmed Isaqali Karobari","doi":"10.1111/omi.70035","DOIUrl":"10.1111/omi.70035","url":null,"abstract":"<p><p>Streptococcus mutans is one of the primary causes of dental caries and is often found in persistent endodontic infections, primarily due to its ability to form acidogenic, aciduric and therapeutically recalcitrant biofilms. The VicRK and LiaSR two-component signal transduction systems (TCS) are particularly important regulators of virulence, envelope integrity and stress response. This paper will provide an updated synthesis of the evidence, at the molecular, genetic and systems levels, regarding the architecture, regulation and integration of VicRK and LiaSR in the control of S. mutans pathogenicity. VicRK helps synthesise essential molecules for biofilm formation and reduces the negative impact of environmental stress on microbes. At the same time, LiaSR responds to antimicrobial peptides, oxidative stress, detergents and root canal irrigants by activating membrane repair and protective stress pathways. Structural, transcriptomic and proteomic studies now indicate extensive regulatory overlap, including overlapping promoter targets, cross-phosphorylation and coordinate regulation of autolysins, cell wall biosynthetic enzymes and extracellular DNA (eDNA) release. These systems all work together as part of the signalling. The ability of S. mutans to survive different pHs, oxidative bursts, lack of nutrients and chemical disinfection in and outside the mouth. According to mutant, knockout and multi-omics studies, these TCSs are critical for biofilm formation, EPS structures, antimicrobial tolerance and interspecies interactions, including synergistic virulence in mixed-species biofilms. As interest in anti-virulence therapeutics grows, drug targets VicRK and LiaSR have emerged. Potential candidates for the selective disruption of TCS signalling that are unlikely to induce resistance include small-molecule inhibitors, marine-derived bioactive compounds and computationally designed ligands. The review also highlights translational gaps and stresses the need for advanced delivery platforms, clinical validation and sustainable production of natural inhibitors. By integrating knowledge of the mechanisms underlying TCS-mediated virulence with available strategies to address it, this review offers a comprehensive overview of this topic.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"241-257"},"PeriodicalIF":3.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13535910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Free Supernatant of Porphyromonas gingivalis Promotes the Malignancy of Oral Squamous Cell Carcinoma by Suppressing Ferroptosis.","authors":"Rongkun Chen, Ruoyu Zhao, Shuyu Zhu, Manhong Zheng, Sijia Ma, Xiaobin Ren, Hongbing He","doi":"10.1111/omi.70039","DOIUrl":"https://doi.org/10.1111/omi.70039","url":null,"abstract":"<p><strong>Background: </strong>Oral squamous cell carcinoma (OSCC) is a series global health concern. Porphyromonas gingivalis (P.g), a major pathogenic bacterium, promotes tumorigenesis and progression. Ferroptosis is also closely related to the progression of tumors. Therefore, this study aimed to investigate whether P.g cell-free supernatant (Pg-SN) alters ferroptosis and malignant phenotypes in OSCC cells.</p><p><strong>Methods: </strong>CCK-8 assays were used to compare the effects of cell-free Pg-SN and Streptococcus salivarius cell-free supernatant (Ss-SN) on OSCC cell viability. Wound healing and Transwell invasion assays were then performed to assess Pg-SN-induced changes in the migratory and invasive abilities. Flow cytometry and fluorescence microscopy were employed to examine ferroptosis biomarkers. Transmission electron microscopy was utilized to observe mitochondrial morphology, while western blot and immunofluorescence analyses were performed to assess ferroptosis-related proteins.</p><p><strong>Results: </strong>Pg-SN enhanced the proliferation, migration, and invasion of OSCC cells. In addition, Pg-SN suppressed ferroptosis in OSCC cells. In comparison, Ss-SN had no significant effect on RSL-3 induced ferroptosis and OSCC cell viability. Furthermore, mechanistic studies demonstrated that Pg-SN modulated the Nrf2/SLC7A11/GPX4 signaling pathway and reduced reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. Pg-SN did not significantly alter TfR1 or ACSL4 expression, suggesting that the suppressive effect on ferroptosis may be independent of iron uptake and ACSL4-dependent lipid remodeling.</p><p><strong>Conclusion: </strong>This study demonstrates that Pg-SN modulates the Nrf2/SLC7A11/GPX4 signaling pathway to suppress ferroptosis and promote the progression of OSCC cells. Targeting P.g associated ferroptosis resistance may represent a potential therapeutic strategy for OSCC.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences Between Oral Neutrophils and Neutrophils Isolated From the Blood of Healthy Donors.","authors":"Svetlana N Pleskova, Nikolay A Bezrukov, Ekaterina D Nikolaeva, Yulia A Zamazkina","doi":"10.1111/omi.70025","DOIUrl":"10.1111/omi.70025","url":null,"abstract":"<p><p>The morphological and viscoelastic properties of blood neutrophils and neutrophils isolated from the oral cavity of the same donor were compared using scanning ion conductance microscopy. It was found that cell morphology, including morphometric parameters (height, diameter, and cell volume), did not differ significantly. However, the elasticity of the membrane-cytoskeletal complex was primarily determined by the cell compartment and its functional state (e.g., migration or adhesion) rather than the neutrophils' ecological niche (blood or oral cavity). The ability of blood neutrophils and oral neutrophils to produce reactive oxygen species (ROS) was assessed using luminol-dependent chemiluminescence. Neutrophils isolated from the oral cavity demonstrated a significantly higher ROS-producing activity compared to blood neutrophils from the same donor. Additionally, oral neutrophils exhibited high variability in ROS production levels, even within the same donor on different days of collection. When comparing the stimulation of ROS production in blood and oral neutrophils exposed to S. aureus 2879M, the cells displayed opposing responses: blood neutrophils were stimulated by Staphylococci, whereas oral neutrophils were inhibited. This response persisted when cells were stimulated by Staphylococci preincubated with saliva. The sequential addition of unfiltered saliva to neutrophils and Staphylococci enhanced this trend, while filtered oral fluid attenuated it. For the first time, it was established that saliva without bacteria (filtered through bacterial filters) suppresses the production of ROS by both blood neutrophils and oral neutrophils, most likely indicating an anti-inflammatory effect of saliva.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"181-187"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porphyromonas gingivalis Outer Membrane Vesicles-Associated DNA Triggers Inflammation by Inducing IL-6 in Astrocytes.","authors":"Ayu Takai, Kaya Yoshida, Yuka Hiroshima, Ayu Ikuta, Mariko Seyama, Yuta Uemura, Hiromichi Yumoto, Kazumi Ozaki","doi":"10.1111/omi.70030","DOIUrl":"10.1111/omi.70030","url":null,"abstract":"<p><p>Porphyromonas gingivalis (Pg), a key pathogen in periodontal disease, is suggested to be involved in the progression of Alzheimer's disease (AD); however, the molecular mechanism remains unclear. We previously reported that Pg-released outer membrane vesicles (OMVs) were detected in the brains of mice after intraperitoneal administration. We here investigated the effects of Pg OMVs on astrocytes, the most abundant glial cells in the central nervous system, which are involved in neuroinflammation. We demonstrated that Pg OMVs increased the expression of interleukin-6 (IL-6) mRNA, which is associated with the pathogenesis of AD, in a Toll-like receptor (TLR)2/4-independent manner in human astrocyte SVG p12 cells. Whole-genome sequencing revealed that Pg OMVs contained Pg genomic DNA, which was critical for IL-6 mRNA induction. The tracking of fluorescent-labeled Pg OMV-associated DNA revealed that Pg OMVs were transported into SVG p12 cells. Endocytosis inhibitors attenuated IL-6 mRNA expression induced by Pg OMVs, suggesting that the incorporation of Pg OMVs by endocytosis is important for IL-6 mRNA induction. Furthermore, the incorporated Pg OMV-associated DNA increased IL-6 mRNA expression via the TLR9 pathway. Our study advances understanding of the role of Pg OMVs, which may contribute to the onset and progression of AD in periodontal disease.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"227-238"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UCHL1 Exacerbates Periodontitis by Coordinating Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Macrophages.","authors":"Yun Yuan, Shengjia Ye, Hanxiao Xue, Xiayue Jin, Xueying Yang, Hongming Zhang, Hui Huang","doi":"10.1111/omi.70028","DOIUrl":"10.1111/omi.70028","url":null,"abstract":"<p><strong>Background: </strong>Given the pivotal role of macrophages in both the progression and regenerative phases of periodontitis, targeting macrophage-mediated immunity represents a novel therapeutic strategy for periodontitis management. Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) has been previously implicated in inflammatory processes. However, how UCHL1 regulates macrophage immune response in periodontitis remains to be elucidated.</p><p><strong>Methods: </strong>Ligature-induced periodontitis mice and Porphyromonas gingivalis lipopolysaccharide (P.g LPS) were used to investigate the expression of UCHL1 in macrophages during immune responses. Lentivirus and an inhibitor were conducted to determine the role of UCHL1 in the periodontitis-associated macrophage immune response. The mitochondrial function and the endoplasmic reticulum status of macrophages were examined to elucidate the underlying mechanisms. Finally, we constructed hydrogels containing UCHL1 inhibitor and evaluated their efficacy in treating periodontitis.</p><p><strong>Results: </strong>The expression of UCHL1 was upregulated in proinflammatory immune response of periodontitis-associated macrophages. Inhibition of UCHL1 reduced the expression and release of TNF-α, IL-6, and IL-1β. In addition, inhibition of UCHL1 in macrophages improved the osteogenesis and migration ability of MC3T3-E1 cells in the co-culture system. Mechanistically, inhibition of UCHL1 ameliorated LPS-induced mitochondrial damage and endoplasmic reticulum stress in macrophages. LDN@GelMA hydrogel had great in vitro anti-inflammatory and bone-promoting effects. Periodontal injection of LDN@GelMA hydrogel alleviated local inflammation and promoted alveolar bone regeneration.</p><p><strong>Conclusions: </strong>Our data suggest that UCHL1 may serve as a critical negative regulator for periodontitis treatment, and inhibition of UCHL1 is expected to improve the periodontal inflammatory microenvironment and promote alveolar bone regeneration.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"201-215"},"PeriodicalIF":3.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}