Document Detail


LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis.
MedLine Citation:
PMID:  16649193     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Human osteoclast formation from mononuclear phagocyte precursors involves interactions between tumor necrosis factor (TNF) ligand superfamily members and their receptors. LIGHT is a transmembrane protein expressed and shed from the surface of activated T cells. Since activated T cells have been implicated in osteoclastogenesis in rheumatoid arthritis (RA), this study sought to determine whether LIGHT can regulate RANKL/cytokine-induced osteoclast formation, to identify the mechanism by which LIGHT influences osteoclastogenesis, and to investigate the presence of LIGHT in the serum of RA patients. METHODS: The effect of LIGHT on human and murine osteoclast formation was assessed in the presence and absence of neutralizing reagents to known osteoclastogenic factors. Serum levels of LIGHT in RA patients were measured by enzyme-linked immunosorbent assay. RESULTS: In the presence and absence of RANKL, LIGHT induced osteoclast formation from both human peripheral blood mononuclear cells and murine macrophage precursors, in a dose-dependent manner, whereas no inhibition was observed by adding osteoprotegerin, RANK:Fc, TNFalpha, or interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or lymphotoxin beta receptor. However, formation of osteoclasts was significantly decreased by the soluble decoy receptor for LIGHT, DcR3, and by blocking antibodies to the p75 component of the TNF receptor. A significant increase in LIGHT levels in the serum of RA patients compared with normal controls was also noted. CONCLUSION: Our results indicate that LIGHT promotes RANKL-mediated osteoclastogenesis and that it can induce osteoclast formation by a mechanism independent of RANKL. The increased concentration of LIGHT in patients with RA raises the possibility that LIGHT may play a role in immunopathogenic conditions that are associated with localized or systemic bone loss.
Authors:
J R Edwards; S G Sun; R Locklin; C M Shipman; I E Adamopoulos; N A Athanasou; A Sabokbar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Arthritis and rheumatism     Volume:  54     ISSN:  0004-3591     ISO Abbreviation:  Arthritis Rheum.     Publication Date:  2006 May 
Date Detail:
Created Date:  2006-05-09     Completed Date:  2006-08-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0370605     Medline TA:  Arthritis Rheum     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1451-62     Citation Subset:  AIM; IM    
Affiliation:
Botnar Research Centre, University of Oxford, Oxford, UK.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arthritis, Rheumatoid / blood*
Bone Resorption / etiology
Carrier Proteins / physiology*
Cells, Cultured
Cytokines / physiology*
Humans
Leukocytes, Mononuclear / physiology
Membrane Glycoproteins / physiology*
Membrane Proteins / blood*,  physiology*
Mice
Osteoclasts / physiology*
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Tumor Necrosis Factor Ligand Superfamily Member 14
Tumor Necrosis Factor-alpha / physiology*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Cytokines; 0/Membrane Glycoproteins; 0/Membrane Proteins; 0/RANK Ligand; 0/Receptor Activator of Nuclear Factor-kappa B; 0/TNFRSF11A protein, human; 0/TNFSF11 protein, human; 0/TNFSF14 protein, human; 0/Tnfrsf11a protein, mouse; 0/Tnfsf11 protein, mouse; 0/Tnfsf14 protein, mouse; 0/Tumor Necrosis Factor Ligand Superfamily Member 14; 0/Tumor Necrosis Factor-alpha

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