B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease

Toshihisa Kawai, Takashi Matsuyama, Yoshitaka Hosokawa, Seicho Makihira, Makoto Seki, Nadeem Y Karimbux, Reginaldo B Goncalves, Paloma Valverde, Serge Dibart, Yi-Ping Li, Leticia A Miranda, Cory W O Ernst, Yuichi Izumi, Martin A Taubman

Research output: Contribution to journalArticlepeer-review

416 Citations (Scopus)


Receptor activator of nuclear factor-kappaB (RANKL)-mediated osteoclastogenesis plays a pivotal role in inflammatory bone resorption. The aim of this study was to identify the cellular source of RANKL in the bone resorptive lesions of periodontal disease. The concentrations of soluble RANKL, but not its decoy receptor osteoprotegerin, measured in diseased tissue homogenates were significantly higher in diseased gingival tissues than in healthy tissues. Double-color confocal microscopic analyses demonstrated less than 20% of both B cells and T cells expressing RANKL in healthy gingival tissues. By contrast, in the abundant mononuclear cells composed of 45% T cells, 50% B cells, and 5% monocytes in diseased gingival tissues, more than 50 and 90% of T cells and B cells, respectively, expressed RANKL. RANKL production by nonlymphoid cells was not distinctly identified. Lymphocytes isolated from gingival tissues of patients induced differentiation of mature osteoclast cells in a RANKL-dependent manner in vitro. However, similarly isolated peripheral blood B and T cells did not induce osteoclast differentiation, unless they were activated in vitro to express RANKL; emphasizing the osteoclastogenic potential of activated RANKL-expressing lymphocytes in periodontal disease tissue. These results suggest that activated T and B cells can be the cellular source of RANKL for bone resorption in periodontal diseased gingival tissue.

Original languageEnglish
Pages (from-to)987-98
Number of pages12
JournalThe American Journal of Pathology
Issue number3
Publication statusPublished - Sept 2006


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