{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:02:22Z","timestamp":1789624942689,"version":"build-2803163510"},"reference-count":35,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2006,10,1]],"date-time":"2006-10-01T00:00:00Z","timestamp":1159660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Periodontology"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Chronic periodontitis is an infectious disease characterized by alveolar bone destruction and teeth loss. Receptor activator of nuclear factor\u2010kappa B ligand (RANKL) is an osteoclastogenic cytokine, a central regulatory factor in the osteoclast's lifespan, and a participant in physiological and pathological bone resorption. Gingival T cells synthesize RANKL, contributing to molecular local imbalance that entails the alveolar bone resorption seen in periodontitis. Our study was aimed at associating the levels of RANKL with the CD4<jats:sup>+<\/jats:sup> T\u2010cell activity present in gingival tissues of chronic periodontitis patients.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Gingival biopsies were obtained from 33 chronic periodontitis patients and 20 healthy controls. Specimens were either formalin fixed and paraffin embedded for real\u2010time reverse transcription\u2010polymerase chain reaction (RT\u2010PCR) and histologic analysis or tissue digestion processed for cell culture and flow\u2010cytometry analysis. RANKL mRNA and protein levels were determined by quantitative RT\u2010PCR and enzyme\u2010linked immunosorbent assay (ELISA) in gingival\u2010cell culture supernatants. Gingival leukocytes were quantified by flow cytometry. RANKL and CD4 immunoreactivity were analyzed by flow cytometry and confocal microscopy.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> RANKL mRNA levels were higher in patients with periodontitis than in healthy subjects, and spontaneous and lipopolysaccharide (LPS)\u2010 and phytohemagglutinin (PHA)\u2010stimulated RANKL synthesis were higher also in patients than controls. CD4<jats:sup>+<\/jats:sup> T lymphocytes were the predominant infiltrate cell subset present in gingival tissues of periodontitis patients. Furthermore, an association between RANKL and CD4<jats:sup>+<\/jats:sup> T cells was determined by double\u2010staining flow cytometry and confocal microscopy.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Taken together, these data demonstrate that gingival CD4<jats:sup>+<\/jats:sup> T cells are the main cells responsible for higher levels of RANKL observed in human chronic periodontitis patients.<\/jats:p>","DOI":"10.1902\/jop.2006.050376","type":"journal-article","created":{"date-parts":[[2006,10,10]],"date-time":"2006-10-10T08:53:03Z","timestamp":1160470383000},"page":"1772-1780","source":"Crossref","is-referenced-by-count":63,"title":["High Expression Levels of Receptor Activator of Nuclear Factor\u2010Kappa B Ligand Associated With Human Chronic Periodontitis Are Mainly Secreted by CD4<sup>+<\/sup> T 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