The DOI matches its Crossref record; 25 of the 25 references it cites were found in a registry or an index.
Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines
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.
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Cites
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Cited by
Estrogen deficiency and bone loss: an inflammatory tale
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Self-citationOsteoimmunology: The conceptual framework unifying the immune and skeletal systems
Okamoto, K., Nakashima, T., Shinohara, M., Negishi-Koga, T., Komatsu, N., Terashima, A., Sawa, S., Nitta, T., & Takayanagi, H. (2017) · Physiological Reviews · doi:10.1152/physrev.00036.2016 · Cited by 534
Regulation of Osteoclast Differentiation by Cytokine Networks
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Cell biology of IL-7, a key lymphotrophin
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Metadata
- Authors
- Weitzmann, M. N., Cenci, S., Rifas, L., Brown, C., & Pacifici, R.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2000-09-01
- Volume
- 96
- Issue
- 5
- Pages
- 1873-1878
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W1555276708
- Cited by
- 265
- References
- 25
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
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- Weitzmann, M. N., Cenci, S., Rifas, L., Brown, C., & Pacifici, R. (2000). Interleukin-7 stimulates osteoclast formation by up-regulating the T-cell production of soluble osteoclastogenic cytokines. Blood. https://doi.org/10.1182/blood.v96.5.1873
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