{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:56:31Z","timestamp":1793213791553,"version":"4.5.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to investigate the role of integrated  stress response (ISR)-related biomarkers in periodontitis (PD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Transcriptomic data related to PD were obtained from public databases. A bioinformatics approach combined with machine learning techniques was used to identify ISR-associated molecular markers involved in PD pathogenesis and to validate their expression patterns. Pathway enrichment analyses and immune landscape characterization were performed to elucidate the molecular mechanisms of these markers in PD progression. Single-cell RNA sequencing (scRNA-seq) was employed to resolve cellular heterogeneity and examine the expression patterns of candidate biomarkers. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assays were conducted to validate the expression profiles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>BTG2, DERL3, FOS, HSPA13, and YOD1 were identified as potential PD biomarkers. Among them, BTG2, DERL3, FOS, and HSPA13 were co-enriched in the \u201costeoclast differentiation\u201d pathway. DERL3 showed the strongest positive correlation with plasma cells and the strongest negative correlation with resting dendritic cells (|cor| &amp;gt; 0.3, P &amp;lt; 0.05). scRNA-seq analysis highlighted T cells as the key population. During T cell differentiation, BTG2 expression initially increased, then decreased, followed by a subsequent rise in the mid-to-late stages; DERL3 expression exhibited a transient increase before returning to baseline; and FOS expression increased gradually throughout the process. RT-qPCR results confirmed that the expression levels of BTG2, DERL3, FOS, and HSPA13 were significantly upregulated, while YOD1 expression was downregulated in the PD group (P &amp;lt; 0.05), which was consistent with the database-predicted patterns.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study integrated bulk and single-cell RNA-seq analyses to identify BTG2, DERL3, FOS, HSPA13, and YOD1 as PD biomarkers, with T cells as the central cell type, providing novel  diagnostic insights for PD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1705047","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:43:52Z","timestamp":1765453432000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Integrative bulk and single-cell transcriptome analyses reveal integrated stress response-related biomarkers in periodontitis with experimental validation"],"prefix":"10.3389","volume":"16","author":[{"given":"Linling","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyi","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2174\/0109298673302701240509103537","article-title":"Hallmarks of periodontitis","volume":"32","author":"Benahmed","year":"2025","journal-title":"Curr Med Chem"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2147\/ijgm.S330724","article-title":"Prevalence and structure of periodontal disease and oral cavity condition in patients with coronary heart disease (Prospective cohort study)","volume":"14","author":"Gor","year":"2021","journal-title":"Int J Gen Med"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2146160","article-title":"Global prevalence of periodontal disease and lack of its surveillance","volume":"2020","author":"Nazir","year":"2020","journal-title":"ScientificWorldJournal"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00774-x","article-title":"Osteoimmunology in periodontitis and orthodontic tooth movement","volume":"21","author":"Alghamdi","year":"2023","journal-title":"Curr Osteoporos Rep"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/idj.12630","article-title":"Current concepts in the management of periodontitis","volume":"71","author":"Kwon","year":"2021","journal-title":"Int Dent J"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-00488-6","article-title":"Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities","volume":"21","author":"Hajishengallis","year":"2021","journal-title":"Nat Rev Immunol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e0237004","DOI":"10.1371\/journal.pone.0237004","article-title":"Salivary microrna 155, 146a\/B and 203: A pilot study for potentially non-invasive diagnostic biomarkers of periodontitis and diabetes mellitus","volume":"15","author":"Al-Rawi","year":"2020","journal-title":"PloS One"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1164667","article-title":"Identification of hub cuproptosis related genes and immune cell infiltration characteristics in periodontitis","volume":"14","author":"Liu","year":"2023","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113829","article-title":"An evidence-based update on the molecular mechanisms underlying periodontal diseases","volume":"21","author":"Qasim","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.Cd-22-1230","article-title":"A ubiquitination cascade regulating the integrated stress response and survival in carcinomas","volume":"13","author":"Cervia","year":"2023","journal-title":"Cancer Discov"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1016\/j.chembiol.2023.10.006","article-title":"Pharmacologic activation of a compensatory integrated stress response kinase promotes mitochondrial remodeling in perk-deficient cells","volume":"30","author":"Perea","year":"2023","journal-title":"Cell Chem Biol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-020-09863-y","article-title":"Perk-eif2\u03b1-atf4 signaling contributes to osteogenic differentiation of periodontal ligament stem cells","volume":"51","author":"Yang","year":"2020","journal-title":"J Mol Histol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/00220345251363525","article-title":"Gcn2-mediated integrated stress response attenuates periodontitis","volume":"22","author":"Huang","year":"2025","journal-title":"J Dent Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1111\/odi.12592","article-title":"Pkr regulates lps-induced osteoclast formation and bone destruction in vitro and in vivo","volume":"23","author":"Teramachi","year":"2017","journal-title":"Oral Dis"},{"key":"B15","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1186\/s12964-025-02372-z","article-title":"The integrated stress response promotes macrophage inflammation and migration in autoimmune diabetes","volume":"23","author":"Wang","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.artmed.2020.101926","article-title":"Dealing with confounders and outliers in classification medical studies: the autism spectrum disorders case study","volume":"108","author":"Ferrari","year":"2020","journal-title":"Artif Intell Med"},{"key":"B17","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1186\/s12859-019-2994-z","article-title":"An elastic-net logistic regression approach to generate classifiers and gene signatures for types of immune cells and T helper cell subsets","volume":"20","author":"Torang","year":"2019","journal-title":"BMC Bioinf"},{"key":"B18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/sam.11300","article-title":"Composite large margin classifiers with latent subclasses for heterogeneous biomedical data","volume":"9","author":"Chen","year":"2016","journal-title":"Stat Anal Data Min"},{"key":"B19","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1080\/10255842.2020.1841754","article-title":"Leveraging machine learning for predicting human body model response in restraint design simulations","volume":"24","author":"Joodaki","year":"2021","journal-title":"Comput Methods Biomech BioMed Engin"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23010052","article-title":"Selecting feature subsets based on svm-rfe and the overlapping ratio with applications in bioinformatics","volume":"23","author":"Lin","year":"2017","journal-title":"Molecules"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1177\/14799731251364875","article-title":"Diagnostic value of peptest\u2122 Combined with gastroesophageal reflux disease questionnaire in identifying patients with gastroesophageal reflux-induced chronic cough","volume":"22","author":"Yuan","year":"2025","journal-title":"Chron Respir Dis"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2023.1179859","article-title":"Mulcnn: an efficient and accurate deep learning method based on gene embedding for cell type identification in single-cell rna-seq data","volume":"14","author":"Jiao","year":"2023","journal-title":"Front Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-023-00777-0","article-title":"Single-cell rna sequencing: technological progress and biomedical application in cancer research","volume":"66","author":"Chang","year":"2024","journal-title":"Mol Biotechnol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7150\/thno.65694","article-title":"Single-cell rna landscape of the osteoimmunology microenvironment in periodontitis","volume":"12","author":"Chen","year":"2022","journal-title":"Theranostics"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1080\/000163501750266747","article-title":"Clinical, pathological and immunological aspects of periodontal disease","volume":"59","author":"Kinane","year":"2001","journal-title":"Acta Odontol Scand"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114236","article-title":"Mapping the tumor stress network reveals dynamic shifts in the stromal oxidative stress response","volume":"43","author":"Lior","year":"2024","journal-title":"Cell Rep"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for rna-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"31072","DOI":"10.1038\/s41598-024-82150-y","article-title":"Effects of moderate intensity exercise on liver metabolism in mice based on multi-omics analysis","volume":"14","author":"Wang","year":"2024","journal-title":"Sci Rep"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Gu","year":"2016","journal-title":"Bioinformatics"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.174277","article-title":"Unraveling the dynamic interplay of microbial communities associated to lupinus angustifolius in response to environmental and cultivation conditions","volume":"946","author":"Ort\u00fazar","year":"2024","journal-title":"Sci Total Environ"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.xinn.2021.100141","article-title":"Clusterprofiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-244","article-title":"Rcircos: an R package for circos 2d track plots","volume":"14","author":"Zhang","year":"2013","journal-title":"BMC Bioinf"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v033.i01","article-title":"Regularization paths for generalized linear models via coordinate descent","volume":"33","author":"Friedman","year":"2010","journal-title":"J Stat Softw"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/nu17010084","article-title":"Gut microbiota interacts with dietary habits in screenings for early detection of colorectal cancer","volume":"17","author":"Vega-Rojas","year":"2024","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s10528-023-10516-4","article-title":"Construction of immune infiltration-related lncrna signatures based on machine learning for the prognosis in colon cancer","volume":"62","author":"Liu","year":"2024","journal-title":"Biochem Genet"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.164212","article-title":"Metagenomic insights into the response of rhizosphere microbial to precipitation changes in the alpine grasslands of northern tibet","volume":"892","author":"Liu","year":"2023","journal-title":"Sci Total Environ"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77","article-title":"Proc: an open-source package for R and S+ to analyze and compare roc curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinf"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1371829","article-title":"Identification and validation of immune-related gene signature models for predicting prognosis and immunotherapy response in hepatocellular carcinoma","volume":"15","author":"Liu","year":"2024","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1192369","article-title":"Prediction of mortality in pneumonia patients with connective tissue disease treated with glucocorticoids or\/and immunosuppressants by machine learning","volume":"14","author":"Li","year":"2023","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/jpm14040410","article-title":"Prediction of acute cardiac rejection based on gene expression profiles","volume":"14","author":"Abdrakhimov","year":"2024","journal-title":"J Pers Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.5534\/wjmh.240131","article-title":"Mitochondrial fis1 as a novel drug target for the treatment of erectile dysfunction: A multi-omic and epigenomic association study","volume":"43","author":"Zhu","year":"2024","journal-title":"World J Mens Health"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","article-title":"Gsva: gene set variation analysis for microarray and rna-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinf"},{"key":"B43","article-title":"Nutrition. 5. Feeding for therapy","volume":"160","author":"Harvey","year":"1985","journal-title":"Nurs Mirror"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.860900","article-title":"Integration of scrna-seq and tcga rna-seq to analyze the heterogeneity of hpv+ and hpv- cervical cancer immune cells and establish molecular risk models","volume":"12","author":"Wei","year":"2022","journal-title":"Front Oncol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.labinv.2023.100263","article-title":"Expression of ido1 in tumor microenvironment significantly predicts the risk of recurrence\/distant metastasis for patients with esophageal squamous cell carcinoma","volume":"103","author":"Qiu","year":"2023","journal-title":"Lab Invest"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28030988","article-title":"Coronavirus inhibitors targeting nsp16","volume":"28","author":"Omer","year":"2023","journal-title":"Molecules"},{"key":"B48","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41587-023-01767-y","article-title":"Dictionary learning for integrative, multimodal and scalable single-cell analysis","volume":"42","author":"Hao","year":"2024","journal-title":"Nat Biotechnol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e22136","DOI":"10.1096\/fj.202101198R","article-title":"Decoding the role of macrophages in periodontitis and type 2 diabetes using single-cell rna-sequencing","volume":"36","author":"Agrafioti","year":"2022","journal-title":"FASEB J"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR120.002155","article-title":"Reactomegsa - efficient multi-omics comparative pathway analysis","volume":"19","author":"Griss","year":"2020","journal-title":"Mol Cell Proteomics"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1038\/s41467-021-21246-9","article-title":"Inference and analysis of cell-cell communication using cellchat","volume":"12","author":"Jin","year":"2021","journal-title":"Nat Commun"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B53","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1111\/prd.12090","article-title":"T- and B-cell subsets in periodontitis","volume":"69","author":"Gonzales","year":"2015","journal-title":"Periodontol 2000"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1007\/s40292-020-00392-z","article-title":"Periodontitis and hypertension: is the association causal","volume":"27","author":"Del Pinto","year":"2020","journal-title":"High Blood Press Cardiovasc Prev"},{"key":"B55","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13024-025-00811-6","article-title":"The integrated stress response in neurodegenerative diseases","volume":"20","author":"Bravo-Jimenez","year":"2025","journal-title":"Mol Neurodegener"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.1263","article-title":"Btg2 is a tumor suppressor gene upregulated by P53 and pten in human bladder carcinoma cells","volume":"7","author":"Tsui","year":"2018","journal-title":"Cancer Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015318","article-title":"Mir-103-3p regulates the proliferation and differentiation of C2c12 myoblasts by targeting btg2","volume":"24","author":"He","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B58","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s12920-024-01915-6","article-title":"Deciphering the molecular nexus of btg2 in periodontitis and diabetic kidney disease","volume":"17","author":"Pan","year":"2024","journal-title":"BMC Med Genomics"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbspin.2022.105471","article-title":"Comment on: \u201cGluten or no gluten for rheumatic diseases?\u201d By philippou E et\u00a0al. Joint bone spine 2022;105453. Doi: 10.1016\/J.Jbspin.2022.105453","volume":"90","author":"Cafaro","year":"2023","journal-title":"Joint Bone Spine"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26216578","article-title":"Synergistic effect of biphasic calcium phosphate and platelet-rich fibrin attenuate markers for inflammation and osteoclast differentiation by suppressing nf-Kb\/mapk signaling pathway in chronic periodontitis","volume":"26","author":"Kumar","year":"2021","journal-title":"Molecules"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.asjsur.2024.06.115","article-title":"The elevated derl3 expression indicates poor prognosis in renal clear cell carcinoma","author":"Fan","year":"2024","journal-title":"Asian J Surg"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2024.116724","article-title":"Kat3b-mediated succinylation of derl3 suppresses osteogenic differentiation by promoting M1\/M2 macrophage polarization","volume":"232","author":"Yu","year":"2025","journal-title":"Biochem Pharmacol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12464","article-title":"Prophylactic supplement with melatonin successfully suppresses the pathogenesis of periodontitis through normalizing rankl\/opg ratio and depressing the tlr4\/myd88 signaling pathway","volume":"64","author":"Renn","year":"2018","journal-title":"J Pineal Res"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1136\/jcp-2023-208931","article-title":"New kids on the block: fos and fosb gene","volume":"76","author":"Cordier","year":"2023","journal-title":"J Clin Pathol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23030615","article-title":"The effects of aronia melanocarpa \u2018Viking\u2019 Extracts in attenuating rankl-induced osteoclastic differentiation by inhibiting ros generation and C-fos\/nfatc1 signaling","volume":"23","author":"Ghosh","year":"2018","journal-title":"Molecules"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.29207","article-title":"Chitooligosaccharide inhibits rankl-induced osteoclastogenesis and ligation-induced periodontitis by suppressing mapk\/C-fos\/nfatc1 signaling","volume":"235","author":"Xu","year":"2020","journal-title":"J Cell Physiol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.14112","article-title":"Lrp5 down-regulation exacerbates inflammation and alveolar bone loss in periodontitis by inhibiting pi3k\/C-fos signalling","volume":"52","author":"Jiang","year":"2025","journal-title":"J Clin Periodontol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.102597","article-title":"Heat shock protein hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation","volume":"298","author":"Espinoza","year":"2022","journal-title":"J Biol Chem"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00913","article-title":"Hspa13 promotes plasma cell production and antibody secretion","volume":"11","author":"He","year":"2020","journal-title":"Front Immunol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"eabh1756","DOI":"10.1126\/sciadv.abh1756","article-title":"Hspa13 facilitates nf-Kb-mediated transcription and attenuates cell death responses in tnf\u03b1 Signaling","volume":"7","author":"Gao","year":"2021","journal-title":"Sci Adv"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.22416","article-title":"Yod1\/traf6 association balances P62-dependent il-1 signaling to nf-Kb","volume":"6","author":"Schimmack","year":"2017","journal-title":"Elife"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/cid.12911","article-title":"Lncrna-mediated cerna network was identified as a crucial determinant of differential effects in periodontitis and periimplantitis by high-throughput sequencing","volume":"22","author":"Zhou","year":"2020","journal-title":"Clin Implant Dent Relat Res"},{"key":"B73","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1111\/jre.12539","article-title":"Integrated analysis of long noncoding rna-associated competing endogenous rna network in periodontitis","volume":"53","author":"Li","year":"2018","journal-title":"J Periodontal Res"},{"key":"B74","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/s12935-025-03881-0","article-title":"Regulation of disease signaling by yod1: potential implications for therapeutic strategies","volume":"25","author":"Zhao","year":"2025","journal-title":"Cancer Cell Int"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-023-05169-x","article-title":"Biomarkers for diagnosis of stage iii, grade C with molar incisor pattern periodontitis in children and young adults: A systematic review and meta-analysis","volume":"27","author":"Alamri","year":"2023","journal-title":"Clin Oral Investig"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.07.165","article-title":"Diagnostic potential and future directions of matrix metalloproteinases as biomarkers in gingival crevicular fluid of oral and systemic diseases","volume":"188","author":"Zhang","year":"2021","journal-title":"Int J Biol Macromol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3390\/dj13090436","article-title":"Salivary biomarker analysis to distinguish between health and periodontitis status: A preliminary study","volume":"13","author":"Bertoldi","year":"2025","journal-title":"Dent J (Basel)"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1007\/s10266-025-01151-z","article-title":"Apical periodontitis and its association with systemic biomarkers: bibliometric analysis of global scientific production and knowledge compilation map","volume":"16","author":"Gomes","year":"2025","journal-title":"Odontology"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3390\/cells11010132","article-title":"Regulation of tnf-induced osteoclast differentiation","volume":"11","author":"Yao","year":"2021","journal-title":"Cells"},{"key":"B80","doi-asserted-by":"publisher","first-page":"e12973","DOI":"10.1111\/cpr.12973","article-title":"Nlrp3 regulates alveolar bone loss in ligature-induced periodontitis by promoting osteoclastic differentiation","volume":"54","author":"Chen","year":"2021","journal-title":"Cell Prolif"},{"key":"B81","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s00774-020-01162-6","article-title":"Osteoclast differentiation by rankl and opg signaling pathways","volume":"39","author":"Udagawa","year":"2021","journal-title":"J Bone Miner Metab"},{"key":"B82","doi-asserted-by":"publisher","first-page":"14239","DOI":"10.1038\/s41598-022-18412-4","article-title":"Effects of extracellular vesicles derived from oral bacteria on osteoclast differentiation and activation","volume":"12","author":"Kim","year":"2022","journal-title":"Sci Rep"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25010010","article-title":"B-cell receptor signaling and beyond: the role of ig\u03b1 (Cd79a)\/ig\u03b2 (Cd79b) in normal and Malignant B cells","volume":"25","author":"Tkachenko","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.892169","article-title":"The ins and outs of antigen uptake in B cells","volume":"13","author":"McShane","year":"2022","journal-title":"Front Immunol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.954936","article-title":"Role of B cells as antigen presenting cells","volume":"13","author":"Rastogi","year":"2022","journal-title":"Front Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041247","article-title":"Endoplasmic reticulum-associated protein degradation","volume":"14","author":"Krshnan","year":"2022","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24043158","article-title":"Regulation of the host immune microenvironment in periodontitis and periodontal bone remodeling","volume":"24","author":"Han","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1177\/00220345221099442","article-title":"Dissecting B\/plasma cells in periodontitis at single-cell\/bulk resolution","volume":"101","author":"Liu","year":"2022","journal-title":"J Dent Res"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-024-00991-0","article-title":"New insights into the ontogeny, diversity, maturation and survival of long-lived plasma cells","volume":"24","author":"Fooksman","year":"2024","journal-title":"Nat Rev Immunol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.01.017","article-title":"Differentiation and maintenance of long-lived plasma cells","volume":"33","author":"Kometani","year":"2015","journal-title":"Curr Opin Immunol"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1177\/0022034519847443","article-title":"Il-37- and il-35\/il-37-producing plasma cells in chronic periodontitis","volume":"98","author":"Jing","year":"2019","journal-title":"J Dent Res"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/j.0906-6713.2004.003560.x","article-title":"Antigen-presentation and the role of dendritic cells in periodontitis","volume":"2000","author":"Cutler","year":"2004","journal-title":"Periodontol"},{"key":"B93","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/prd.12428","article-title":"Dendritic cells a critical link to alveolar bone loss and systemic disease risk in periodontitis: immunotherapeutic implications","volume":"89","author":"El-Awady","year":"2022","journal-title":"Periodontol 2000"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2015.140643","article-title":"Odanacatib, a cathepsin K-specific inhibitor, inhibits inflammation and bone loss caused by periodontal diseases","volume":"86","author":"Hao","year":"2015","journal-title":"J Periodontol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.1046451","article-title":"A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy","volume":"13","author":"Li","year":"2022","journal-title":"Front Pharmacol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/187873","article-title":"Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice","volume":"2013","author":"Xu","year":"2013","journal-title":"Mediators Inflammation"},{"key":"B97","doi-asserted-by":"publisher","first-page":"20190814","DOI":"10.3390\/ijms20163949","article-title":"T and B cells in periodontal disease: new functions in a complex scenario","volume":"20","author":"Figueredo","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.108797","article-title":"Immunotherapy with regulatory T and B cells in periodontitis","volume":"109","author":"Zou","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2005.76.10.1675","article-title":"T cells support osteoclastogenesis in an in vitro model derived from human periodontitis patients","volume":"76","author":"Brunetti","year":"2005","journal-title":"J Periodontol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1002\/jper.17-0674","article-title":"Memory T cell subsets in healthy gingiva and periodontitis tissues","volume":"89","author":"Mahanonda","year":"2018","journal-title":"J Periodontol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1705047\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T11:43:58Z","timestamp":1765453438000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1705047\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":100,"alternative-id":["10.3389\/fimmu.2025.1705047"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1705047","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"article-number":"1705047"}}