Nature medicine, 2004-06, Vol.10 (6), p.617-624
2004
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- Autor(en) / Beteiligte
- Titel
- Selective inhibition of NF-κB blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo
- Ist Teil von
- Nature medicine, 2004-06, Vol.10 (6), p.617-624
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2004
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Bone destruction is a pathological hallmark of several chronic inflammatory diseases, including rheumatoid arthritis and periodontitis. Inflammation-induced bone loss of this sort results from elevated numbers of bone-resorbing osteoclasts. Gene targeting studies have shown that the transcription factor nuclear factor-kappa B (NF-kappa B) has a crucial role in osteoclast differentiation, and blocking NF-kappa B is a potential strategy for preventing inflammatory bone resorption. We tested this approach using a cell-permeable peptide inhibitor of the I kappa B-kinase complex, a crucial component of signal transduction pathways to NF-kappa B. The peptide inhibited RANKL-stimulated NF-kappa B activation and osteoclastogenesis both in vitro and in vivo. In addition, this peptide significantly reduced the severity of collagen-induced arthritis in mice by reducing levels of tumor necrosis factor-alpha and interleukin-1 beta, abrogating joint swelling and reducing destruction of bone and cartilage. Therefore, selective inhibition of NF-kappa B activation offers an effective therapeutic approach for inhibiting chronic inflammatory diseases involving bone resorption.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1078-8956eISSN: 1546-170XDOI: 10.1038/nm1054Titel-ID: cdi_proquest_miscellaneous_71968345
- Format
- –
- Schlagworte
- Animals, Arthritis, Experimental - immunology, Arthritis, Experimental - metabolism, Arthritis, Experimental - pathology, Bone and Bones - cytology, Bone and Bones - metabolism, Bone and Bones - pathology, Bone Marrow Cells - cytology, Bone Marrow Cells - metabolism, Bone Resorption - immunology, Bone Resorption - metabolism, Carrier Proteins - metabolism, Cell Differentiation - physiology, Cells, Cultured, I-kappa B Proteins - antagonists & inhibitors, Inflammation - immunology, Inflammation - metabolism, Interleukin-1 - metabolism, Macrophages - cytology, Macrophages - metabolism, Male, Membrane Glycoproteins - metabolism, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, NF-kappa B - antagonists & inhibitors, NF-kappa B - metabolism, Osteoclasts - physiology, Peptides - metabolism, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B, Signal Transduction - physiology, Tumor Necrosis Factor-alpha - metabolism