LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis

J. R. Edwards, S. G. Sun, R. Locklin, C. M. Shipman, Iannis Adamopoulos, N. A. Athanasou, A. Sabokbar

Research output: Contribution to journalArticle

65 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1451-1462
Number of pages12
JournalArthritis and Rheumatism
Volume54
Issue number5
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

Bone Resorption
Rheumatoid Arthritis
Light
Osteoclasts
Osteogenesis
Receptors, Tumor Necrosis Factor, Member 6b
Receptors, Tumor Necrosis Factor, Member 14
Tumor Necrosis Factors
Serum
T-Lymphocytes
Osteoprotegerin
Lymphotoxin-alpha
Blocking Antibodies
Tumor Necrosis Factor Receptors
Phagocytes
Interleukin-8
Blood Cells
Tumor Necrosis Factor-alpha
Enzyme-Linked Immunosorbent Assay
Macrophages

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

Edwards, J. R., Sun, S. G., Locklin, R., Shipman, C. M., Adamopoulos, I., Athanasou, N. A., & Sabokbar, A. (2006). LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis. Arthritis and Rheumatism, 54(5), 1451-1462. https://doi.org/10.1002/art.21821

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 journalArticle

Edwards, JR, Sun, SG, Locklin, R, Shipman, CM, Adamopoulos, I, Athanasou, NA & Sabokbar, A 2006, 'LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis', Arthritis and Rheumatism, vol. 54, no. 5, pp. 1451-1462. https://doi.org/10.1002/art.21821
Edwards, J. R. ; Sun, S. G. ; Locklin, R. ; Shipman, C. M. ; Adamopoulos, Iannis ; Athanasou, N. A. ; Sabokbar, A. / LIGHT (TNFSF14), a novel mediator of bone resorption, is elevated in rheumatoid arthritis. In: Arthritis and Rheumatism. 2006 ; Vol. 54, No. 5. pp. 1451-1462.
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AU - Sun, S. G.

AU - Locklin, R.

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AU - Adamopoulos, Iannis

AU - Athanasou, N. A.

AU - Sabokbar, A.

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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.

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