B and T Lymphocytes Are the Primary Sources of RANKL in the Bone Resorptive Lesion of Periodontal Disease (original) (raw)
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Journal of Periodontology, 2004
Background: Receptor activator of nuclear factor κB ligand (RANK-L) is a cytokine involved in the regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis. One of the major causes of tooth loss in humans is bone destruction. The aim of our study was to determine the presence of RANK-L in gingival crevicular fluid (GCF) samples from adult patients with untreated chronic periodontitis and in healthy controls. We also identified the RANK-L present in lesions undergoing episodic attachment loss from GCF. Methods: GCF samples were collected from two periodontally affected sites (probing depth ≥5 mm, attachment loss ≥3 mm) in 20 patients (N = 40). After monitoring for 4 months, seven patients showed active periodontal disease, and GCF samples were collected from one active and one inactive site (N = 14 samples). The comparison with healthy controls was carried out by collecting GCF samples from 12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip, and enzymelinked immunosorbent assay (ELISA) was performed to determine the total amount of RANK-L. Results: RANK-L was found in a higher proportion (85%) of samples from patients than from controls (46%). The total amount of RANK-L was significantly higher in patients (115.53 ± 78.18 picograms [pg]) than in healthy subjects (63.08 ± 55.08 pg) (P = 0.003). Active sites, presumably associated with tissue destruction, had significantly higher levels of RANK-L than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007). Conclusion: GCF total amount of RANK-L is significantly increased in periodontal disease, supporting its role in the alveolar bone loss developed in this disease.
Clinical & Experimental Immunology, 2007
Periodontal disease involves multi-bacterial infections accompanied by inflammatory bone resorption lesions. The abundant T and B lymphocyte infiltrates are the major sources of the osteoclast differentiation factor, receptor activator for nuclear factor-kB ligand (RANKL) which, in turn, contributes to the development of bone resorption in periodontal disease. In the present study, we found that the concentrations of RANKL and regulatory T cell (Treg)-associated cytokine, interleukin (IL)-10, in the periodontal tissue homogenates were correlated negatively, whereas RANKL and proinflammatory cytokine, IL-1b, showed positive correlation. Also, according to the fluorescent-immunohistochemistry, the frequency of forkhead box P3 (FoxP3)/CD25 double-positive cells was diminished strikingly in the bone resorption lesion of periodontal disease compared to healthy gingival tissue, while CD25 or FoxP3 single positive cells were still observed in lesions where abundant RANKL + lymphocytes were present. Very importantly, few or no expressions of FoxP3 by the RANKL + lymphocytes were observed in the diseased periodontal tissues. Finally, IL-10 suppressed both soluble RANKL (sRANKL) and membrane RANKL (mRANKL) expression by peripheral blood mononuclear cells (PBMC) activated in vitro in a bacterial antigenspecific manner. Taken together, these results suggested that FoxP3/CD25 double-positive Treg cells may play a role in the down-regulation of RANKL expression by activated lymphocytes in periodontal diseased tissues. This leads to the conclusion that the phenomenon of diminished CD25 + FoxP3 + Treg cells appears to be associated with the increased RANKL + T cells in the bone resorption lesion of periodontal disease.
Journal of Periodontal Research, 2007
Background and Objective: Receptor activator of nuclear factor-jB ligand (RANKL) is responsible for the induction of osteoclastogenesis and bone resorption, whereas its decoy receptor, osteoprotegerin, can directly block this action. Because this dyad of cytokines is crucial for regulating the bone remodelling process, imbalances in their expression may cause a switch from the physiological state to enhanced bone resorption or formation. This study investigated the mRNA expression of RANKL and osteoprotegerin, as well as their relative ratio, in the gingival tissues of patients with various forms of periodontal diseases.
Critical Reviews in Oral Biology & Medicine, 2001
Periodontal disease is a peripheral infection involving species of Gram-negative organisms. T-lymphocytes can be found in the dense inflammatory infiltrate in this disease. CD4+ and CD8+ T-cells are present in periodontal lesions, as are memory/activated T-lymphocytes. In addition, Th Iand Th2-type T-lymphocytes and their associated cytokines with a subtle polarization to Th 1 may be present. Th 1-type T-cells up-regulate the production of pro-inflammatory cytokines IL-1 and TNF-cx, which can induce bone resorption indirectly by promoting differentiation of osteoclast precursors and subsequently by activating osteoclasts. Such osteoclast differentiation is dependent on stimulation of osteoprotegerin ligand (OPG-L) production by osteoblastic cells. By contrast, activated T-cells, by virtue of direct production and expression of OPG-L, can directly promote osteoclast differentiation. OPG-L appears to be predominantly expressed on Th I -type cells. The direct and indirect T-cell involvement in periodontal bone resorption appears to be dependent on the degree of Th 1-type T-cell recruitment into inflamed gingival tissues. This T-cell recruitment is regulated by adhesion molecules and chemokines/chemokine receptors. The adhesion molecules involved include cx4 and cx6 integrins, LFA-1, and ICAM-1. The Th I -type T-cells preferentially express CCR5 and CXCR3, which are found prominently in diseased gingivae. By contrast, little CCR4, expressed by Th2-type T-cells, can be detected. Also, the chemokine ligands RANTES, MIPl-cx (both CCR5), and IP-10 (CXCR3 ligand) were elevated in inflamed periodontal tissues. The T-cell features in diseased periodontal tissues can be compared with those in rheumatoid arthritis, wherein bone resorption often attributed to Thl-type T-cell involvement has also been demonstrated. ration of the disease by the administration of the immunosuppressant drugs, cyclosporin A or FK506, in patients (van den Borne et al., 12(2):125 135 (2001) Grit Rev Oral Biol Med 131 131 Crit Rev Oral Biol Med 1 2(2):l1 25-1 35 (2001 ) Association of localized juvenile periodontitis (LJP) with serum antibody responses to Actinobacillus actinomycetemcomi-132 Crit Rev Oral Biol Med (2uul) 132 Crit Rev Oral Biol Med 12(2):125-135 (2001) toxic effector function. I Immunol 153:2302-231 1. Macatonia SE, Hosken NA, Litton M, Vieira P, Hsieh C-S, 12.2I125-135 (2001) Crit Rev Oral Biol Med 133 133 Crit Rev Oral Biol Med 134 Crit Rev Oral Biol Med 12(2):125-135 (2001) 12(2)125 155 (2UU1) Crit Rev Oral Biol Med 135 135 Crit Rev Oral Biol Med
Periodontitis is a destructive disease that targets tooth-supporting structures through complex and multifactorial pathogenic processes. Alveolar bone destruction, a hallmark of periodontitis progression and one of the major causes of tooth loss in human, is mediated by the host immune and inflammatory response to microbial challenge. The discovery of the receptor activator of nuclear factor-kappa B (RANK)/ RANK ligand (RANKL)/osteoprotegerin (OPG) axis has improved the knowledge of bone metabolism regulation. The RANKL/RANK interaction is needed for differentiation and maturation of osteoclast precursor cells to activate osteoclasts and for the survival of mature osteoclasts. Osteoprotegerin is the naturally occurring inhibitor of osteoclast differentiation. It binds to RANKL with high affinity and blocks RANKL from interacting with RANK. The RANKL/OPG ratio is increased in periodontitis compared to healthy individuals, suggesting that this molecular interaction may be important in modulating local bone loss.
Journal of Periodontology, 2004
Background: Receptor activator of nuclear factor κB ligand (RANK-L) is a cytokine involved in the regulation of osteoclastogenesis in bone remodeling and inflammatory osteolysis. One of the major causes of tooth loss in humans is bone destruction. The aim of our study was to determine the presence of RANK-L in gingival crevicular fluid (GCF) samples from adult patients with untreated chronic periodontitis and in healthy controls. We also identified the RANK-L present in lesions undergoing episodic attachment loss from GCF. Methods: GCF samples were collected from two periodontally affected sites (probing depth ≥5 mm, attachment loss ≥3 mm) in 20 patients (N = 40). After monitoring for 4 months, seven patients showed active periodontal disease, and GCF samples were collected from one active and one inactive site (N = 14 samples). The comparison with healthy controls was carried out by collecting GCF samples from 12 healthy volunteers (N = 24 samples). GCF was collected using a paper strip, and enzymelinked immunosorbent assay (ELISA) was performed to determine the total amount of RANK-L. Results: RANK-L was found in a higher proportion (85%) of samples from patients than from controls (46%). The total amount of RANK-L was significantly higher in patients (115.53 ± 78.18 picograms [pg]) than in healthy subjects (63.08 ± 55.08 pg) (P = 0.003). Active sites, presumably associated with tissue destruction, had significantly higher levels of RANK-L than their inactive counterparts (125.95 pg versus 91.80 pg, P = 0.007). Conclusion: GCF total amount of RANK-L is significantly increased in periodontal disease, supporting its role in the alveolar bone loss developed in this disease.
Journal of Periodontal Research, 2003
Little is known about the process of alveolar bone loss that occurs in periodontitis. The inflammation and tissue destruction seen in periodontitis is associated with granulomatous tissue containing inflammatory cells, such as T and B lymphocytes, plasma cells and many cells of the monocytes/macrophage lineage. These cells are thought to produce a variety of inflammatory mediators. High levels of several inflammatory cytokines, such as inter-leukin-1a (IL-1a), IL-b, IL-6, prostaglandin E 2 (PGE 2) and tumour necrosis factor a (TNFa), have been found in the tissue and gingival crevicular fluid of patients suffering advanced periodontitis (1-4). Similar