B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease.
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.
Kawai
Toshihisa
T
Department of Immunology, The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA.
Matsuyama
Takashi
T
Hosokawa
Yoshitaka
Y
Makihira
Seicho
S
Seki
Makoto
M
Karimbux
Nadeem Y
NY
Goncalves
Reginaldo B
RB
Valverde
Paloma
P
Dibart
Serge
S
Li
Yi-Ping
YP
Miranda
Leticia A
LA
Ernst
Cory W O
CW
Izumi
Yuichi
Y
Taubman
Martin A
MA
D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001862:Bone Resorption / Q000276:immunology* / Q000473:pathology; D002352:Carrier Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology; D005881:Gingiva / Q000276:immunology / Q000473:pathology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D018613:Microscopy, Confocal; D010010:Osteoclasts / Q000276:immunology / Q000473:pathology; D053244:Osteoprotegerin; D010518:Periodontitis / Q000276:immunology* / Q000473:pathology; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human