Abstract
IL-23, a clinically novel cytokine, targets CD4(+) T cells. Recent IL-1Ra(-/-) mouse studies have demonstrated that IL-23 indirectly stimulates the differentiation of osteoclast precursors by enhancing IL-17 release from CD4(+) T cells. IL-17, in turn, stimulates osteoclastogenesis in osteoclast precursor cells. In this study, we found that IL-23 up-regulates receptor activator of NF-kappaB ligand expression by CD4(+) T cells, and thus contributes to osteoclastogenesis. This indirect pathway is mediated by NF-kappaB and STAT3. We have also demonstrated that IL-23 can influence osteoclastogenesis positively under the special conditions in the IL-1-dominant milieu of IL-1Ra(-/-) mice. We propose that IL-23-enhanced osteoclastogenesis is mediated mainly by CD4(+) T cells. The results of this study show that IL-23 is a promising therapeutic target for the treatment of arthritis-associated bone destruction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arthritis, Experimental / immunology
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Arthritis, Experimental / metabolism*
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Arthritis, Experimental / physiopathology
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CD4-Positive T-Lymphocytes / metabolism*
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Cells, Cultured
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Disease Models, Animal
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Disease Progression
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Interleukin-23 / immunology
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Interleukin-23 / metabolism*
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Joints / immunology
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Joints / metabolism
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Mice
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Mice, Knockout
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NF-kappa B / immunology
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NF-kappa B / metabolism
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Osteoclasts / cytology
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Osteoclasts / immunology
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Osteoclasts / metabolism*
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RANK Ligand / immunology
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RANK Ligand / metabolism*
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Receptor Activator of Nuclear Factor-kappa B / immunology
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Receptor Activator of Nuclear Factor-kappa B / metabolism*
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STAT3 Transcription Factor / immunology
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Up-Regulation
Substances
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Interleukin-23
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NF-kappa B
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RANK Ligand
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Receptor Activator of Nuclear Factor-kappa B
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Tnfrsf11a protein, mouse
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Tnfsf11 protein, mouse