Inflammation最新文献

{"title":"Toll-like Receptors 1, 3 and 7 Activate Distinct Genetic Features of NF-κB Signaling and γ-Protocadherin Expression in Human Cardiac Fibroblasts.","authors":"Aditi Chaudhari, Camila Axelsson, Lillemor Mattsson Hultén, Victoria Rotter Sopasakis","doi":"10.1007/s10753-025-02238-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02238-z","url":null,"abstract":"<p><p>Fibroblasts play a pivotal role in key processes within the heart, particularly in cardiac remodeling that follows both ischemic and non-ischemic injury. During remodeling, fibroblasts drive fibrosis and inflammation by reorganizing the extracellular matrix and modulating the immune response, including toll-like receptor (TLR) activation, to promote tissue stabilization. Building on findings from our prior research on heart tissue from patients with advanced coronary artery disease and aortic valve disease, this study sought to explore specific effects of TLR1, TLR3, and TLR7 activation on NF-κB signaling, proinflammatory cytokine production, and γ-protocadherin expression in cardiac fibroblasts. Human cardiac fibroblasts were exposed to agonists for TLR1, TLR3, or TLR7 for 24 h, followed by an analysis of NF-κB signaling, cytokine production, and γ-protocadherin expression. The activation of these TLRs triggered distinct responses in the NF-κB signaling pathway, with TLR3 showing a stronger activation profile compared to TLR1 and TLR7, particularly in downregulating γ-protocadherin expression. These findings highlight a potential role for TLR3 in amplifying inflammatory responses and reducing γ-protocadherin levels in cardiac fibroblasts, correlating with the enhanced inflammation and lower γ-protocadherin expression observed in diseased myocardium from patients with coronary artery disease and aortic valve disease. Consequently, TLR3 represents a potential therapeutic target for modulating immune responses in cardiovascular diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Activation of the NLRP3 Inflammasome Is Associated with Valosin-Containing Protein Myopathy.","authors":"Angèle Nalbandian, Arif A Khan, Ruchi Srivastava, Katrina J Llewellyn, Baichang Tan, Nora Shukr, Yasmin Fazli, Virginia E Kimonis, Lbachir BenMohamed","doi":"10.1007/s10753-025-02246-z","DOIUrl":"https://doi.org/10.1007/s10753-025-02246-z","url":null,"abstract":"","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular Senescence Contributes to Colonic Barrier Integrity Impairment Induced by Toxoplasma gondii Infection.","authors":"Yingting Huang, Yumeng Zhou, Zhicheng He, Jiayi Yang, Jianqi Gu, Bingqian Cui, Siyu Li, Heng Deng, Wendi Zhao, Xiaoying Yang, Fenfen Sun, Cheng He, Wei Pan","doi":"10.1007/s10753-024-02213-0","DOIUrl":"https://doi.org/10.1007/s10753-024-02213-0","url":null,"abstract":"<p><p>Toxoplasma gondii (T. gondii) induces gut barrier integrity impairment, which is crucial to the establishment of long-term infection in hosts. Cellular senescence is an imperative event that drives disease progression. Several studies have indicated that T. gondii induces oxidative stress and cell cycle blockade in the tissues of hosts, suggesting cellular senescence induced by the parasite. Here, we explored whether cell senescence is involved in T. gondii-mediated colonic barrier integrity damage in mice. C57BL/6J mice were infected with 10 cysts of T. gondii. Senolytic therapy (dasatinib and quercetin, DQ, a combination therapy for reducing senescent cells) was given by oral gavage 4 weeks post-infection. Alcian blue staining, immunofluorescence, western blot, quantitative PCR (qPCR), and enzyme-linked immunosorbent assay (ELISA) were employed to evaluate the thickness of the colonic mucus layer, the expression profiles of genes and proteins related to tight junction function and cellular senescence in the colonic tissues, and the levels of serum lipopolysaccharides (LPS), respectively. T. gondii-infected mice exhibited deteriorated secreted mucus, shortened length, decreased expression of zonula occludens-1 (ZO-1) and occludin in the colon, accompanied by elevated levels of serum LPS. Moreover, the infection upregulated cell senescence-related markers (p16^INK4A, p21^CIP1) while inhibiting Lamin B1 expression. In addition, the expression levels of senescence-associated secretory phenotypes (SASPs), including IL-1β, TNF-α, IL-6, MMP9 and CXCL10, were upregulated post-infection. Notably, reducing cell senescence with DQ administration, significantly ameliorated the colonic pathological alterations induced by T. gondii infection. This study uncovers for the first time that cellular senescence contributes to the colonic barrier integrity damage induced by chronic T. gondii infection. Importantly, we provide evidence that senolytic therapy exerts a therapeutic effect on the intestinal pathological lesions.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silencing of lncRNA Gm26917 Attenuates Alveolar Macrophage-mediated Inflammatory Response in LPS-induced Acute Lung Injury Via Inhibiting NKRF Ubiquitination.","authors":"Yuanyuan Zhang, Chunai Zhan, Long Mei, Xinyu Li, Weiyi Liu, Mengfei Sheng, Yaoyun Wang, Qing Zhao, Lizhi Zhang, Min Shao, Wei Shao","doi":"10.1007/s10753-025-02240-5","DOIUrl":"https://doi.org/10.1007/s10753-025-02240-5","url":null,"abstract":"<p><p>The inflammatory response mediated by alveolar macrophages plays a crucial role in the development of acute lung injury. Numerous studies have reported that lncRNAs are highly expressed in acute lung injury in mouse models and cell lines, and acute lung injury (ALI) can be effectively alleviated by targeting these lncRNAs. The aim of this study was to explore the mechanism by LncRNA Gm26917 regulates the inflammatory response in alveolar macrophages during acute lung injury mouse model. We initially observed a significant upregulation of Gm26917 expression in both ALI conditions and in MH-S cells treated with LPS. Furthermore, the silencing of Gm26917 via lentivirus-mediated methods conferred protection against LPS-induced ALI. Additionally, siRNA-mediated knockdown of Gm26917 attenuated LPS-induced inflammatory responses and modulated the function of alveolar macrophages. Subsequent mechanistic studies revealed that Gm26917 interacts with NKRF, and its knockdown suppressed NKRF ubiquitination, thereby enhancing NKRF binding to p50 and subsequently inhibiting the NF-κB signaling pathway. In conclusion, our findings demonstrate that silencing Gm26917 can mitigate LPS-induced ALI by modulating the NF-κB signaling pathway in alveolar macrophages through interactions with NKRF.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-selectin Promotes Migration, Invasion and Inflammatory Response of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis via NF-kB Signaling Pathway.","authors":"Weijie Wu, Zhen Cheng, Yunyi Nan, Gang Pan, Youhua Wang","doi":"10.1007/s10753-025-02242-3","DOIUrl":"https://doi.org/10.1007/s10753-025-02242-3","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease characterized by chronic inflammation of the synovium and progressive joint damage. Fibroblast-like synoviocytes (FLSs) exhibit excessive proliferative and aggressive phenotypes and play a major role in the pathophysiology of RA. Previous studies have confirmed the pathologic role of L-selectin in cell adhesion and migration. In rheumatoid arthritis models, L-selectin regulates leukocyte homing, which leads to joint inflammation. Moreover, in L-selectin knockout mice, there is a reduction in joint inflammation. However, the associations of L-selectin with FLSs in RA remain unclear. This study aims to reveal the effect of L-selectin on RA-FLSs and to investigate the molecular mechanism of L-selectin in RA. Our findings indicated that L-selectin was significantly expressed in RA synovial tissues and RA-FLSs. L-selectin silencing reduced RA-FLSs migration and invasion and attenuated the secretion of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in vitro. Moreover, investigations into mechanisms revealed that L-selectin activated the nuclear factor kappa-B (NF-κB) signaling pathway while blocking this signaling pathway could compromise the effects of L-selectin. Finally, in vivo experiments with a collagen-induced arthritis rat model revealed that silencing L-selectin alleviated inflammatory infiltration of the synovium and cartilage destruction, and validated the NF-κB signaling pathways findings observed in vitro. In summary, we show that L-selectin enhances the migration and invasion of RA-FLSs through the activation of NF-κB signaling pathways, ultimately worsening the progression of RA.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143004702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical Anti-Inflammatory Effects of Quercetin Glycosides on Atopic Dermatitis-Like Lesions: Influence of the Glycone Type on Efficacy and Skin Absorption.","authors":"Shih-Chun Yang, Zi-Yu Chang, Chien-Yu Hsiao, Abdullah Alshetaili, Shih-Hsuan Wei, Yu-Tai Hsiao, Jia-You Fang","doi":"10.1007/s10753-025-02236-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02236-1","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a multifaceted inflammatory skin condition characterized by the involvement of various cell types, such as keratinocytes, macrophages, neutrophils, and mast cells. Research indicates that flavonoids possess anti-inflammatory properties that may be beneficial in the management of AD. However, the investigation of the glycoside forms for anti-AD therapy is limited. We aimed to assess the ability of quercetin-3-O-glycosides in treating AD-like lesions through in silico-, cell-, and animal-based platforms. The glycosylated flavonols of quercitrin, isoquercitrin, and rutin were used in this study. We also tried to understand the influence of glycone type on the bioactivity and skin delivery of glycosides. The glycosides effectively reduced the overexpression of proinflammatory effectors such as interleukin (IL)-6, chemokine (C-X-C motif) ligand (CXCL)1, CXCL8, regulated upon activation normal T cell expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC) in the activated keratinocytes. This reduction could be due to the inhibition of extracellular signal-regulated kinase (ERK) and p38 phosphorylation. Isoquercitrin (but not quercitrin and rutin) could arrest the upregulated IL-6 and CCL5 in the macrophage model. The glycosides significantly prevented histamine release from RBL-2H3 cells. The skin absorption examination showed a greater permeation of quercitrin and isoquercitrin than rutin with dual sugar moieties due to the smaller molecular volume and higher lipophilicity. The skin deposition of quercitrin and isoquercitrin was enhanced by about 11-fold in the stripped and delipidized skins, which mimicked AD lesions. The in vivo dinitrochlorobenzene (DNCB)-induced AD mouse model demonstrated less erosion, scaling, and epidermal hyperplasia after topical isoquercitrin treatment. The concentration of cytokines/chemokines in the lesion was decreased by isoquercitrin. These effects were similar to those of tacrolimus ointment. The immunohistochemistry (IHC) displayed the reduction of epidermal hyperproliferation and immune cell infiltration by topical isoquercitrin. The results indicated that the delivery of quercetin glycosides could provide an efficient and safe way to treat AD inflammation.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Mitochondrial Succinate Dehydrogenase with Dimethyl Malonate Promotes M2 Macrophage Polarization by Enhancing STAT6 Activation.","authors":"Chaowen He, Pengfei Chen, Luwen Ning, Xiuping Huang, Huimin Sun, Yuanyuan Wang, Yanli Zhao, Changchun Zeng, Dongsheng Huang, Hanchao Gao, Mengtao Cao","doi":"10.1007/s10753-024-02207-y","DOIUrl":"https://doi.org/10.1007/s10753-024-02207-y","url":null,"abstract":"<p><p>Macrophages exhibit diverse phenotypes depending on environment status, which contribute to physiological and pathological processes of immunological diseases, including sepsis, asthma, multiple sclerosis and colitis. The alternative activation of macrophages is tightly regulated to avoid excessive activation and damage of tissues and organs. Certain works characterized that succinate dehydrogenase (SDH) altered function of macrophages and promoted inflammatory response in M1 macrophages via mitochondrial reactive oxygen species (ROS). However, the effect of succinate dehydrogenase on M2 macrophage polarization remains incompletely understood. We employed dimethyl malonate (DMM) to inhibit succinate dehydrogenase activity and took use of RNA-seq to analyze the changes of inflammatory response of LPS-activated M1 macrophages or IL 4-activated M2 macrophages. Our data revealed that inhibition of SDH with DMM increased expression of M2 macrophages-associated signature genes, including Arg1, Ym1 and Mrc1. Consistent with previous work, we also observed that inhibition of SDH decreased the expression of IL-1β and enhanced the levels of IL-10 in M1 macrophages. Additionally, inhibition of SDH with DMM inhibited the production of chemokines, such as Cxcl3, Cxcl12, Ccl20 and Ccl9. DMM also amplified the M2 macrophages-related signature genes in IL-13-activated M2 macrophages. Mechanistic studies revealed that DMM promoted M2 macrophages polarization through mitochondrial ROS dependent STAT6 activation. Blocking ROS with mitoTEMPO or inhibiting STAT6 activation with ruxolitinib abrogated the promotion effect of DMM on M2 macrophages. Finally, dimethyl malonate treatment promoted peritoneal M2 macrophages differentiation and exacerbated OVA-induced allergy asthma in vivo. Collectively, we identified SDH as a braker to suppress M2 macrophage polarization via mitochondrial ROS, suggesting a novel strategy to treatment of M2 macrophages-mediated inflammatory diseases.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Construction of a R-loop Mediated Diagnostic Model and Associated Immune Microenvironment of COPD through Machine Learning and Single-Cell Transcriptomics.","authors":"Jianing Lin, Yayun Nan, Jingyi Sun, Anqi Guan, Meijuan Peng, Ziyu Dai, Suying Mai, Qiong Chen, Chen Jiang","doi":"10.1007/s10753-024-02232-x","DOIUrl":"https://doi.org/10.1007/s10753-024-02232-x","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) is a prevalent chronic inflammatory airway disease with high incidence and significant disease burden. R-loops, functional chromatin structure formed during transcription, are closely associated with inflammation due to its aberrant formation. However, the role of R-loop regulators (RLRs) in COPD remains unclear. Utilizing both bulk transcriptome data and single-cell RNA sequencing data, we assessed the diverse expression patterns of RLRs in the lung tissues of COPD patients. A lower R-loop score was found in patients with COPD and in neutrophils. 12 machine learning algorithms (150 combinations) identified 14 hub RLRs (CBX8, EHD4, HDLBP, KDM6B, NFAT5, NLRP3, NUP214, PAFAH1B3, PINX1, PLD1, POLB, RCC2, RNF213, and VIM) associated with COPD. A RiskScore based on 14 RLRs identified two distinct COPD subtypes. Patient groups at high risk of COPD (low R-loop scores) had a higher immune score and a significant increase in neutrophils in their immune microenvironment compared to low-risk groups. PD-0325901 and QL-X-138 represent prospective COPD treatments for high-risk (low R-loop score) and low-risk (high R-loop score) patients. Finally, RT-PCR experiments confirmed expression differences of 8 RLRs (EHD4, HDLBP, NFAT5, NLRP3, PLD1, PINX1, POLB, and VIM) in COPD mice lung tissue. R-loops significantly contribute to the development of COPD and constructing predictive models based on RLRs may provide crucial insight into personalized treatment strategies for patients with COPD.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Piezo1-Induced Nasal Epithelial Barrier Dysfunction in Allergic Rhinitis.","authors":"Shengyang Liu, Jianhua Wu, Linghui Meng, Yuan Liu, Jinzhuang Yu, Jing Yue, Dingqian Hao, Peng Yu, YuZhu Wan, Ping Li, Peng Jin, Li Shi","doi":"10.1007/s10753-024-02234-9","DOIUrl":"https://doi.org/10.1007/s10753-024-02234-9","url":null,"abstract":"<p><p>This study aimed to investigate the role of Piezo1 in nasal epithelial barrier dysfunction in allergic rhinitis (AR) using both in vitro and in vivo experimental methods. A total of 79 human nasal mucosal samples were collected, including 43 from AR patients and 36 from healthy controls. Additionally, 12 BALB/c mice were used for the in vivo experiments. Human nasal epithelial cells (HNEpCs) were employed for the in vitro studies. In the in vivo study, mice were sensitized with ovalbumin (OVA) to induce AR. In the in vitro experiments, Piezo1 expression in HNEpCs was silenced using shRNA, followed by stimulation with IL-13. The expression of Piezo1, ERK1/2, and tight junctions (TJs) components (including ZO-1, Occludin, and Claudin-1) was assessed using quantitative RT-PCR, immunofluorescence, and Western blotting. Statistical analyses included paired Student's t-test and one-way ANOVA. Piezo1 expression was significantly elevated in both AR patients and OVA-induced AR mice, while TJs components were significantly reduced (p < 0.05). Knockdown of Piezo1 in HNEpCs restored the levels of TJs and improved barrier integrity. A negative correlation between Piezo1 and ERK1/2 expression was observed. Piezo1 plays a crucial role in nasal epithelial barrier dysfunction in AR by modulating TJs and the ERK1/2 pathway. These findings suggest that Piezo1 may serve as a potential therapeutic target for AR.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dnmt3a-mediated DNA Methylation Regulates P. gingivalis-suppressed Cementoblast Mineralization Partially Via Mitochondria-dependent Apoptosis Pathway.","authors":"Heyu Liu, Li Ma, Huiyi Wang, Xin Huang, Yan Peng, Zhengkun Yang, Junhong Xiao, Hantao Huang, Qiudong Yang, Jiahui Sun, Xiaoxuan Wang, Chuan Wang, Liu Yang, Zhengguo Cao","doi":"10.1007/s10753-024-02235-8","DOIUrl":"https://doi.org/10.1007/s10753-024-02235-8","url":null,"abstract":"<p><strong>Background: </strong>DNA methyltransferase 3A (Dnmt3a) is an enzyme that catalyzes the de novo methylation of DNA, and plays essential roles in a wide range of physiological and pathological processes. However, it remains unclear whether Porphyromonas gingivalis affects cementoblasts, the cells responsible for cementum formation, through Dnmt3a.</p><p><strong>Methods: </strong>The samples were collected from models of mouse periapical lesions and mice of different ages, and the expression of Dnmt3a was detected through immunofluorescence. Porphyromonas gingivalis was co-cultured with cementoblasts that simultaneously overexpressed Dnmt3a. Additionally, cementoblasts were subjected to either Dnmt3a knockout or DNA methylation inhibition. Changes in global DNA methylation were analyzed, and quantitative PCR, western blotting, alkaline phosphatase (ALP) activity assays, and Alizarin Red staining were employed to evaluate alterations in the mineralization capacity of cementoblasts.RNA sequencing further showed the mechanisms by which Dnmt3a regulated mineralization. Flow cytometry, MitoSox, and TRMR staining were used to verify the participation of mitochondria-dependent apoptosis.</p><p><strong>Results: </strong>The effect of P. gingivalis on Dnmt3a and global DNA methylation in cementoblasts was first verified. Dnmt3a expression and global DNA methylation were upregulated during cementoblast mineralization. Samples with periapical inflammation exhibited reduced Dnmt3a expression. P. gingivalis stimulation reduced the global DNA methylation and the mineralization ability of cementoblasts. Both the knockdown of Dnmt3a and using DNA methylation inhibitors suppressed cementoblast mineralization. In addition, Dnm3a depletion was significantly correlated with the mitochondria-dependent apoptosis pathway in cementoblasts.</p><p><strong>Conclusions: </strong>P. gingivalis blocks DNA methylation by silencing Dnmt3a in cementoblasts, thereby inducing mitochondrial-dependent apoptosis and, ultimately, impaired cementogenesis.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142948221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}