{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:46:44Z","timestamp":1785833204973,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>MicroRNAs (miRNAs) have been proposed as promising biomarkers for periodontal disease because of their role in regulating inflammation and tissue remodeling. This study evaluated the salivary expressions of miR-34a, miR-155, and miR-146a and their relationships with periodontal disease and its clinical severity. Saliva samples were collected from 35 patients with periodontal disease and 35 healthy controls, and miRNA expression was quantified by quantitative real-time PCR (qRT-PCR). Fold-change values were log2-transformed, and analyses included differential expression (Mann\u2013Whitney U with Benjamini\u2013Hochberg correction), Spearman correlation with clinical attachment loss (CAL), logistic regression\/ROC modeling with internal cross-validation, and an exploratory differential co-expression analysis. None of the three miRNAs was significantly differentially expressed between groups (all FDR-adjusted p &gt; 0.40; the result was unchanged after adjustment for age), and none correlated with CAL after accounting for the healthy-versus-diseased separation. miR-34a showed poor stand-alone diagnostic performance (AUC = 0.58; five-fold cross-validation 0.56). Patients were significantly older than controls (41.1 vs. 37.1 years; p &lt; 0.001), and age was the strongest single discriminator (AUC = 0.82), indicating that age acts as an important confounder. In an exploratory analysis, the positive co-expression observed among the three miRNAs in healthy controls was attenuated in disease (e.g., miR-155\/miR-146a Spearman rho = 0.68 vs. 0.27; permutation p approximately 0.06). These findings indicate that salivary miR-34a, miR-155 and miR-146a abundance do not discriminate periodontitis in this cohort, but underline age as a critical confounder and suggest that altered miRNA co-expression, rather than differential abundance, may warrant further investigation in larger, age-matched studies. In addition, miR-34a and miR-146a showed reduced expression dispersion in disease; because the reduced dispersion and the reduced co-expression cannot be fully separated in a sample of this size, these network-level observations are regarded as jointly hypothesis-generating.<\/jats:p>","DOI":"10.3390\/cells15151392","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T01:43:27Z","timestamp":1785721407000},"page":"1392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salivary microRNA Expression and Co-Expression Patterns in Periodontal Disease: A Cross-Sectional Analysis of miR-34a, miR-155 and miR-146a"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4548-5515","authenticated-orcid":false,"given":"Elena-Teodora","family":"T\u00e2lvan","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5725-662X","authenticated-orcid":false,"given":"Liviu\u021ba","family":"Budi\u0219an","sequence":"additional","affiliation":[{"name":"Department of Genomics, MEDFUTURE Institute for Biomedical Research, Iuliu Ha\u021bieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u0103lin Ilie","family":"Mohor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3997-1691","authenticated-orcid":false,"given":"Valentin","family":"Grecu","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, \u201cLucian Blaga\u201d University of Sibiu, 550025 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5828-1325","authenticated-orcid":false,"given":"Ioana","family":"Berindan-Neagoe","sequence":"additional","affiliation":[{"name":"Department of Genomics, MEDFUTURE Institute for Biomedical Research, Iuliu Ha\u021bieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3055-4747","authenticated-orcid":false,"given":"Cornelia","family":"Braicu","sequence":"additional","affiliation":[{"name":"Department of Genomics, MEDFUTURE Institute for Biomedical Research, Iuliu Ha\u021bieganu University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2965-3713","authenticated-orcid":false,"given":"George C\u0103lin","family":"Oprinca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cosmin-Ioan","family":"Mohor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian Nicolae","family":"Cristian","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cLucian Blaga\u201d University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/odi.14436","article-title":"The Global Burden of Periodontal Diseases in 204 Countries and Territories from 1990 to 2019","volume":"30","author":"Zhang","year":"2024","journal-title":"Oral Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/sj.ebd.6401037","article-title":"Review Finds That Severe Periodontitis Affects 11% of the World Population","volume":"15","author":"Richards","year":"2014","journal-title":"Evid. Based Dent."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/JPER.21-0111","article-title":"Economic Burden of Periodontitis in the United States and Europe: An Updated Estimation","volume":"93","author":"Botelho","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/prd.12617","article-title":"Periodontal Diseases in Africa","volume":"98","author":"Olujitan","year":"2024","journal-title":"Periodontol. 2000"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.1002\/JPER.21-0625","article-title":"The Spatial and Temporal Trends of Severe Periodontitis Burden in Asia, 1990-2019: A Population-Based Epidemiological Study","volume":"93","author":"Luo","year":"2022","journal-title":"J. Periodontol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"38","DOI":"10.54133\/ajms.v7i2.1364","article-title":"The Impact of Age and Gender on Periodontal Conditions in Iraqi People: A Retrospective Study","volume":"7","author":"Alwan","year":"2024","journal-title":"AL-Rafidain J. Med. Sci."},{"key":"ref_7","first-page":"1","article-title":"Expression of Interleukin (IL)-1\u03b2, IL-8, IL-10 and IL-13 in Chronic Adult Periodontitis Progression","volume":"9","author":"Mohor","year":"2017","journal-title":"Arch. Med."},{"key":"ref_8","first-page":"17","article-title":"Role of Gender & Age in Chronic Periodontal Disease","volume":"16","author":"Jain","year":"2021","journal-title":"Hormones"},{"key":"ref_9","first-page":"7403042","article-title":"Gender Variations in the Oral Microbiomes of Elderly Patients with Initial Periodontitis","volume":"2021","author":"Zhao","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"75","DOI":"10.9734\/ca\/2024\/v13i1395","article-title":"A Comprehensive Review on Biomarker and Its Role in Diseases","volume":"13","author":"Sireesha","year":"2024","journal-title":"Cardiol. Angiol. Int. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"476","DOI":"10.53350\/pjmhs2023176476","article-title":"Prospective Biomarker-Based Strategies for Early Diagnosis and Management of Periodontal Diseases: A Clinical Observational Study","volume":"17","author":"Mansoor","year":"2023","journal-title":"Pak. J. Med. Health Sci."},{"key":"ref_12","first-page":"373","article-title":"Correlation of Chronic Periodontitis Progression with sTREM-1 and E-Cadherin Salivary Levels","volume":"26","author":"Mohor","year":"2018","journal-title":"Rev. Romana Med. Lab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"77","DOI":"10.18231\/j.ijpi.2024.017","article-title":"Salivary Biomarkers\u2013Emerging Era in Periodontics","volume":"9","author":"S","year":"2024","journal-title":"IP Int. J. Periodontol. Implantol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1007\/s10238-024-01334-y","article-title":"Exploring Regulatory Mechanisms on miRNAs and Their Implications in Inflammation-Related Diseases","volume":"24","author":"Nalbant","year":"2024","journal-title":"Clin. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7065","DOI":"10.3390\/cimb46070421","article-title":"Expression and Functional Analysis of Immuno-Micro-RNAs Mir-146a and Mir-326 in Colorectal Cancer","volume":"46","author":"Farc","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e1121","DOI":"10.1002\/iid3.1121","article-title":"Exploring the Theranostic Potentials of miRNA and Epigenetic Networks in Autoimmune Diseases: A Comprehensive Review","volume":"11","author":"Nag","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"110063","DOI":"10.1016\/j.abb.2024.110063","article-title":"MiR-34a Promotes Mitochondrial Pathway of Apoptosis in Human Salivary Gland Epithelial Cells by Activating NF-\u03baB Signaling","volume":"758","author":"He","year":"2024","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_18","first-page":"1279","article-title":"Cellular Senescence with SASP in Periodontal Ligament Cells Triggers Inflammation in Aging Periodontal Tissue","volume":"15","author":"Ikegami","year":"2023","journal-title":"Aging"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Raucci, A., and Vinci, M.C. (2020). miR-34a: A Promising Target for Inflammaging and Age-Related Diseases. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218293"},{"key":"ref_20","first-page":"6670","article-title":"Expression of miR-155 and miR-146a in the Saliva of Patients with Periodontitis and Its Clinical Value","volume":"13","author":"Wu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"111214","DOI":"10.1016\/j.humimm.2024.111214","article-title":"Role of miRNA-155 in Macrophage Polarisation in Stage III\/IV Periodontitis with Type II Diabetes Mellitus: An Analytical Case-Control Study","volume":"86","author":"Mathews","year":"2025","journal-title":"Hum. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"39","DOI":"10.4103\/1735-3327.344162","article-title":"Comparative Evaluation of microRNA-155 Expression Level and Its Correlation with Tumor Necrotizing Factor \u03b1 and Interleukin 6 in Patients with Chronic Periodontitis","volume":"19","author":"Mogharehabed","year":"2022","journal-title":"Dent. Res. J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.imlet.2020.07.008","article-title":"A Comprehensive Review on miR-146a Molecular Mechanisms in a Wide Spectrum of Immune and Non-Immune Inflammatory Diseases","volume":"227","author":"Aslani","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.bbadis.2017.12.035","article-title":"miR-146a Regulates Inflammatory Cytokine Production in Porphyromonas Gingivalis Lipopolysaccharide-Stimulated B Cells by Targeting IRAK1 but Not TRAF6","volume":"1864","author":"Jiang","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"R64","DOI":"10.1186\/gb-2009-10-6-r64","article-title":"A Novel and Universal Method for microRNA RT-qPCR Data Normalization","volume":"10","author":"Mestdagh","year":"2009","journal-title":"Genome Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S130","DOI":"10.1111\/jcpe.12944","article-title":"Age-dependent Distribution of Periodontitis in Two Countries: Findings from NHANES 2009 to 2014 and SHIP-TREND 2008 to 2012","volume":"45","author":"Billings","year":"2018","journal-title":"J. Clin. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.tig.2010.05.001","article-title":"From \u2018Differential Expression\u2019 to \u2018Differential Networking\u2019\u2013Identification of Dysfunctional Regulatory Networks in Diseases","volume":"26","year":"2010","journal-title":"Trends Genet."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Amar, D., Safer, H., and Shamir, R. (2013). Dissection of Regulatory Networks That Are Altered in Disease via Differential Co-Expression. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1002955"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/nrg1990","article-title":"The Evolution of Gene Regulation by Transcription Factors and microRNAs","volume":"8","author":"Chen","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"T\u00e2lvan, C.-D., T\u00e2lvan, E.-T., Mohor, C.I., Budi\u0219an, L., Grecu, V., Mihalache, M., Neagoe, I.B., Z\u0103noag\u0103, O., Oprinca, G.C., and Cristian, A.N. (2025). The Impact of miRNA Expression on Colon Cancer Severity, Invasiveness, and Localization. Cancers, 17.","DOI":"10.3390\/cancers17071091"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1038\/nature03702","article-title":"MicroRNA Expression Profiles Classify Human Cancers","volume":"435","author":"Lu","year":"2005","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1146\/annurev-immunol-020711-075013","article-title":"microRNA Regulation of Inflammatory Responses","volume":"30","author":"Rao","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Santonocito, S., Polizzi, A., Palazzo, G., and Isola, G. (2021). The Emerging Role of microRNA in Periodontitis: Pathophysiology, Clinical Potential and Future Molecular Perspectives. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115456"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1177\/0022034512456551","article-title":"MicroRNAs and Their Target Genes in Gingival Tissues","volume":"91","author":"Guarnieri","year":"2012","journal-title":"J. Dent. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1111\/prd.12095","article-title":"Mini but Mighty: Micro RNA s in the Pathobiology of Periodontal Disease","volume":"69","author":"Kebschull","year":"2015","journal-title":"Periodontol. 2000"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"157","DOI":"10.2334\/josnusd.56.157","article-title":"MicroRNA-146a and microRNA-155 Show Tissue-Dependent Expression in Dental Pulp, Gingival and Periodontal Ligament Fibroblasts in Vitro","volume":"56","author":"Sipert","year":"2014","journal-title":"J. Oral Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1007\/s10266-025-01299-8","article-title":"MicroRNAs as Diagnostic Biomarkers in Periodontitis: A Systematic Review and Meta-Analysis","volume":"114","author":"Memon","year":"2026","journal-title":"Odontology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1093\/nar\/gks1030","article-title":"Differential Activation and Functional Specialization of miR-146 and miR-155 in Innate Immune Sensing","volume":"41","author":"Schulte","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Testa, U., Pelosi, E., Castelli, G., and Labbaye, C. (2017). miR-146 and miR-155: Two Key Modulators of Immune Response and Tumor Development. Non-Coding RNA, 3.","DOI":"10.3390\/ncrna3030022"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:22:53Z","timestamp":1785831773000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/15\/1392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,31]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15151392"],"URL":"https:\/\/doi.org\/10.3390\/cells15151392","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,31]]}}}