Abstract
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, TNFα, or interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or lymphotoxin β 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1451-1462 |
| Number of pages | 12 |
| Journal | Arthritis and Rheumatism |
| Volume | 54 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis. / Edwards, J. R.; Sun, S. G.; Locklin, R.; Shipman, C. M.; Adamopoulos, Iannis; Athanasou, N. A.; Sabokbar, A.
In: Arthritis and Rheumatism, Vol. 54, No. 5, 05.2006, p. 1451-1462.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis
AU - Edwards, J. R.
AU - Sun, S. G.
AU - Locklin, R.
AU - Shipman, C. M.
AU - Adamopoulos, Iannis
AU - Athanasou, N. A.
AU - Sabokbar, A.
PY - 2006/5
Y1 - 2006/5
N2 - 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, TNFα, or interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or lymphotoxin β 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.
AB - 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, TNFα, or interleukin-8 or by blocking the LIGHT receptors herpesvirus entry mediator or lymphotoxin β 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.
UR - http://www.scopus.com/inward/record.url?scp=33646494179&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646494179&partnerID=8YFLogxK
U2 - 10.1002/art.21821
DO - 10.1002/art.21821
M3 - Article
C2 - 16649193
AN - SCOPUS:33646494179
VL - 54
SP - 1451
EP - 1462
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 5
ER -