{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:37:21Z","timestamp":1785418641742,"version":"3.56.0"},"reference-count":32,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017218","name":"Giresun University","doi-asserted-by":"publisher","award":["SA\u011e-BAP-A-240222-47"],"award-info":[{"award-number":["SA\u011e-BAP-A-240222-47"]}],"id":[{"id":"10.13039\/100017218","id-type":"DOI","asserted-by":"publisher"}]},{"award":["SA\u011e-BAP-A-240222-47"],"award-info":[{"award-number":["SA\u011e-BAP-A-240222-47"]}],"id":[{"id":"https:\/\/ror.org\/05szaq822","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: This study aimed to evaluate the gingival crevicular fluid (GCF) levels of fractalkine\/CX3CL1 and CX3CR1 in patients with gingivitis and periodontitis before and after non-surgical periodontal therapy. Methods: A total of 90 individuals comprising 30 with stage 3 periodontitis, 30 with gingivitis, and 30 periodontally healthy, were enrolled in the study. Gingivitis and periodontitis patients underwent non-surgical periodontal treatment. GCF samples were collected at baseline and at 1 and 3 months after treatment. CX3CL1 and CX3CR1 were measured by an ELISA analysis. Results: GCF CX3CL1 and CX3CR1 were significantly elevated in patients with periodontitis and gingivitis compared to healthy controls (p &lt; 0.001). The periodontitis patients also showed higher GCF levels of CX3CL1 and CX3CR1 than those with gingivitis (p &lt; 0.001). Significant decreases in GCF CX3CL1 and CX3CR1 were detected at 1 month after periodontal treatment compared to baseline values in both the gingivitis and periodontitis patients (p &lt; 0.001). Moreover, the periodontitis patients exhibited significant decreases in both CX3CL1 and CX3CR1 levels at 3 months post-treatment compared to 1 month (p &lt; 0.001), whereas no significant changes were observed between the two time points in the gingivitis patients (p &gt; 0.05). Conclusions: Our findings suggest that the CX3CL1\u2013CX3CR1 axis might contribute to the inflammatory processes of periodontal diseases and may represent a treatment-responsive component of the local host response.<\/jats:p>","DOI":"10.3390\/jcm15134922","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:48:16Z","timestamp":1782366496000},"page":"4922","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fractalkine and CX3CR1 Levels in Gingivitis and Stage 3 Periodontitis Patients Following Non-Surgical Periodontal Therapy: A Prospective Clinical Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9139-8752","authenticated-orcid":false,"given":"Zeynep Pinar Keles","family":"Yucel","sequence":"first","affiliation":[{"name":"Department of Periodontology, Faculty of Dentistry, Giresun University, 28200 Giresun, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahattin","family":"Avci","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, Ondokuz Mayis University, 55270 Samsun, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1902\/jop.2008.080213","article-title":"Mapping the Pathogenesis of Periodontitis: A New Look","volume":"79","author":"Kornman","year":"2008","journal-title":"J. Periodontol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1034\/j.1600-0757.2000.2240110.x","article-title":"Regulators of tissue destruction and homeostasis as diagnostic aids in periodontology","volume":"24","author":"Kinane","year":"2000","journal-title":"Periodontology 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/jcpe.12782","article-title":"Natural history of periodontitis: Disease progression and tooth loss over 40 years","volume":"44","author":"Ramseier","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/jcpe.12690","article-title":"Gingivitis and lifestyle influences on high-sensitivity C-reactive protein and interleukin 6 in adolescents","volume":"44","author":"Pitchika","year":"2017","journal-title":"J. Clin. Periodontol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1111\/prd.12146","article-title":"Molecular basis for immunohistochemical and inflammatory changes during progression of gingivitis to periodontitis","volume":"76","author":"Kurgan","year":"2018","journal-title":"Periodontology 2000"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1034\/j.1600-0765.2003.02012.x","article-title":"Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease","volume":"38","author":"Garlet","year":"2003","journal-title":"J. Periodontal Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/cyto.2002.1985","article-title":"The presence of chemokine (MCP-1, MIP-1\u03b1, MIP-1\u03b2, IP-10, RANTES)-positive cells and chemokine receptor (CCR5, CXCR3)-positive cells in inflamed human gingival tissues","volume":"20","author":"Kabashima","year":"2002","journal-title":"Cytokine"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1080\/14397595.2016.1213481","article-title":"Fractalkine\/CX3CL1 in rheumatoid arthritis","volume":"27","author":"Nanki","year":"2017","journal-title":"Mod. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.4110\/in.2018.18.e5","article-title":"Tissue-specific Role of CX3CR1 Expressing Immune Cells and Their Relationships with Human Disease","volume":"18","author":"Lee","year":"2018","journal-title":"Immune Netw."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0092-8674(00)80438-9","article-title":"Identification and molecular characterization of fractalkine receptor CX(3)CR1, which mediates both leukocyte migration and adhesion","volume":"91","author":"Imai","year":"1997","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1084\/jem.188.8.1413","article-title":"Fractalkine and CX3CR1 mediate a novel mechanism of leukocyte capture, firm adhesion, and activation under physiologic flow","volume":"188","author":"Fong","year":"1998","journal-title":"J. Exp. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"7825","DOI":"10.4049\/jimmunol.0803627","article-title":"Role of CX3CL1\/Fractalkine in Osteoclast Differentiation and Bone Resorption","volume":"183","author":"Koizumi","year":"2009","journal-title":"J. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1181","DOI":"10.1002\/iid3.1181","article-title":"The role of the CX3CL1\/CX3CR1 axis as potential inflammatory biomarkers in subjects with periodontitis and rheumatoid arthritis: A systematic review","volume":"12","author":"Mosaddad","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"964","DOI":"10.7150\/ijms.49460","article-title":"STAT3\/miR-15a-5p\/CX3CL1 Loop Regulates Proliferation and Migration of Vascular Endothelial Cells in Atherosclerosis","volume":"18","author":"Li","year":"2021","journal-title":"Int. J. Med. Sci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cormican, S., and Griffin, M.D. (2021). Fractalkine (CX3CL1) and Its Receptor CX3CR1: A Promising Therapeutic Target in Chronic Kidney Disease?. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.664202"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1002\/JPER.20-0632","article-title":"Salivary and serum concentrations of monocyte chemoattractant protein-1, macrophage inhibitory factor, and fractalkine in relation to rheumatoid arthritis and periodontitis","volume":"92","author":"Yilmaz","year":"2021","journal-title":"J. Periodontol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"155117","DOI":"10.1016\/j.cyto.2020.155117","article-title":"Upregulation of circulating inflammatory biomarkers under the influence of periodontal disease in rheumatoid arthritis patients","volume":"131","author":"Panezai","year":"2020","journal-title":"Cytokine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/jre.12859","article-title":"Potential biomarkers reflecting inflammation in patients with severe periodontitis: Fractalkine (CX3CL1) and its receptor (CX3CR1)","volume":"56","author":"Balci","year":"2021","journal-title":"J. Periodontal Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"155197","DOI":"10.1016\/j.cyto.2020.155197","article-title":"Chemokines and cytokines profile in whole saliva of patients with periodontitis","volume":"135","author":"Kawamoto","year":"2020","journal-title":"Cytokine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1365-2249.2005.02675.x","article-title":"Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, in periodontal diseased tissue","volume":"139","author":"Hosokawa","year":"2005","journal-title":"Clin. Exp. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/JPER.23-0692","article-title":"Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health","volume":"95","author":"Hsu","year":"2024","journal-title":"J. Periodontol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3109\/00016356309011240","article-title":"Periodontal disease in pregnancy I. Prevalence and severity","volume":"21","author":"Silness","year":"1963","journal-title":"Acta Odontol. Scand."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3109\/00016356408993968","article-title":"Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition","volume":"22","author":"Silness","year":"1964","journal-title":"Acta Odontol. Scand."},{"key":"ref_24","first-page":"229","article-title":"Problems and proposals for recording gingivitis and plaque","volume":"25","author":"Ainamo","year":"1975","journal-title":"Int. Dent. J."},{"key":"ref_25","first-page":"S74","article-title":"Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Chapple","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_26","first-page":"S173","article-title":"Periodontitis: Consensus report of Workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Papapanou","year":"2018","journal-title":"J. Periodontol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1111\/prd.12107","article-title":"Gingival crevicular fluid as a source of biomarkers for periodontitis","volume":"70","author":"Barros","year":"2016","journal-title":"Periodontology 2000"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bibi, T., Khurshid, Z., Rehman, A., Imran, E., Srivastava, K.C., and Shrivastava, D. (2021). Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases. Molecules, 26.","DOI":"10.3390\/molecules26051208"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"241","DOI":"10.2147\/ITT.S277991","article-title":"Emerging Role of Fractalkine in the Treatment of Rheumatic Diseases","volume":"9","author":"Tanaka","year":"2020","journal-title":"Immunotargets Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3007148","DOI":"10.1155\/2024\/3007148","article-title":"Salivary Fractalkine Differentiating Periodontitis from Periodontally Healthy Subjects","volume":"2024","author":"Harbood","year":"2024","journal-title":"Int. J. Dent."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1002\/jcp.25577","article-title":"Involvement of CX3CL1 in the Migration of Osteoclast Precursors Across Osteoblast Layer Stimulated by Interleukin-1\u00df","volume":"232","author":"Matsuura","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1080\/14397595.2017.1337056","article-title":"Safety, pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody, in a first-in-patient phase 1\/2 study on rheumatoid arthritis","volume":"28","author":"Tanaka","year":"2018","journal-title":"Mod. Rheumatol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4922\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T04:18:11Z","timestamp":1782965891000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/13\/4922"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,24]]},"references-count":32,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15134922"],"URL":"https:\/\/doi.org\/10.3390\/jcm15134922","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,24]]}}}