Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines

M. N. Weitzmann, S. Cenci, L. Rifas, C. Brown, R. Pacifici

Research output: Contribution to journalArticle

185 Citations (Scopus)

Abstract

In unstimulated conditions osteoclast renewal occurs as a result of the stromal cell production of the key osteoclastogenic factors, receptor activator of NFkB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Inflammation is known to cause increased osteoclastogenesis; however, the mechanisms responsible for this phenomenon are poorly understood. We now show that interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFα), cytokines typically produced in inflammatory conditions, increase the stromal cell production of IL-7. This factor, in turn, up-regulates production of osteoclastogenic cytokines by T cells leading to stimulation of osteoclast (OC) formation. Although T cells were found to produce soluble forms of both RANKL and M-CSF, saturating concentrations of osteoprotegerin failed to inhibit approximately 40% of the OC formation, suggesting that IL-7 acts via both RANKL-dependent and RANKL-independent pathways. Despite the identification of T-cell-secreted M-CSF, this cytokine was not essential for either RANKL-dependent or -independent OC formation, suggesting that T cells secrete other cytokines capable of substituting for M-CSF action. On the basis of our data, we propose a novel mechanism for inflammatory bone loss in which induction of IL-7 from stromal cells by IL-1 and TNFα leads to the production of soluble osteoclastogenic cytokines by T cells. Thus, the mechanism by which IL-7 causes bone resorption involves the activation of T cells and the T-cell-dependent augmentation of osteoclastogenesis. (C) 2000 by The American Society of Hematology.

Original languageEnglish
Pages (from-to)1873-1878
Number of pages6
JournalBlood
Volume96
Issue number5
Publication statusPublished - Sep 1 2000

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Interleukin-7
T-cells
Osteoclasts
Cytokines
Macrophage Colony-Stimulating Factor
T-Lymphocytes
Ligands
Stromal Cells
Interleukin-1
Osteogenesis
Bone
Tumor Necrosis Factor-alpha
Osteoprotegerin
Bone Resorption
Up-Regulation
Chemical activation
Inflammation
Bone and Bones

ASJC Scopus subject areas

  • Hematology

Cite this

Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. / Weitzmann, M. N.; Cenci, S.; Rifas, L.; Brown, C.; Pacifici, R.

In: Blood, Vol. 96, No. 5, 01.09.2000, p. 1873-1878.

Research output: Contribution to journalArticle

Weitzmann, M. N. ; Cenci, S. ; Rifas, L. ; Brown, C. ; Pacifici, R. / Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. In: Blood. 2000 ; Vol. 96, No. 5. pp. 1873-1878.
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