The Journal of clinical investigation, 2005-02, Vol.115 (2), p.282-290
2005
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- Autor(en) / Beteiligte
- Titel
- IL-1 mediates TNF-induced osteoclastogenesis
- Ist Teil von
- The Journal of clinical investigation, 2005-02, Vol.115 (2), p.282-290
- Ort / Verlag
- United States: American Society for Clinical Investigation
- Erscheinungsjahr
- 2005
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- TNF-induced receptor activator NF-kappaB ligand (RANKL) synthesis by bone marrow stromal cells is a fundamental component of inflammatory osteolysis. We found that this process was abolished by IL-1 receptor antagonist (IL-1Ra) or in stromal cells derived from type I IL-1 receptor-deficient (IL-1RI-deficient) mice. Reflecting sequential signaling of the cytokines TNF and IL-1, TNF induces stromal cell expression of IL-1 and IL-1RI. These data suggest that TNF regulates RANKL expression via IL-1, and, therefore, IL-1 plays a role in TNF-induced periarticular osteolysis. Consistent with this posture, TNF-stimulated osteoclastogenesis in cultures consisting of WT marrow macrophages and stromal cells exposed to IL-1Ra or in cocultures established with IL-1RI-deficient stromal cells was reduced approximately 50%. The same magnitude of osteoclast inhibition occurred in IL-1RI-deficient mice following TNF administration in vivo. Like TNF, IL-1 directly targeted osteoclast precursors and promoted the osteoclast phenotype in a TNF-independent manner in the presence of permissive levels of RANKL. IL-1 is able to induce RANKL expression by stromal cells and directly stimulate osteoclast precursor differentiation under the aegis of p38 MAPK. Thus, IL-1 mediates the osteoclastogenic effect of TNF by enhancing stromal cell expression of RANKL and directly stimulating differentiation of osteoclast precursors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9738eISSN: 1558-8238DOI: 10.1172/JCI200523394Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_544608
- Format
- –
- Schlagworte
- Animals, Biomedical research, Bone marrow, Bone Marrow Cells - cytology, Bone Marrow Cells - physiology, Carrier Proteins, Cell Differentiation - genetics, Cell Differentiation - physiology, Cells, Cultured, Coculture Techniques, Cytokines, Gene expression, Gene Expression Regulation - genetics, Gene Expression Regulation - physiology, Interleukin-1 - physiology, Ligands, Macrophages - physiology, MAP Kinase Signaling System - genetics, MAP Kinase Signaling System - physiology, Membrane Glycoproteins, Mice, Mice, Knockout, Osteoclasts - physiology, Osteolysis - genetics, Osteolysis - psychology, p38 Mitogen-Activated Protein Kinases - metabolism, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Interleukin-1 - genetics, Receptors, Interleukin-1 - metabolism, Receptors, Interleukin-1 Type I, Rheumatoid arthritis, Stem Cells - physiology, Stromal Cells, Tumor Necrosis Factor-alpha - physiology