Requirement of the inducible nitric oxide synthase pathway for IL-1-induced osteoclastic bone resorption
| Autor: | Foo Y. Liew, R. J. van't Hof, L. M Smith, Kenneth J. Armour, Xiao-Qing Wei, Katharine E. Armour, Stuart H. Ralston |
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| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
Parathyroid hormone Nitric Oxide Synthase Type II Osteoclasts Bone Marrow Cells Bone resorption Nitric oxide Bone remodeling Immunoenzyme Techniques chemistry.chemical_compound Mice Osteoclast Internal medicine Bone cell medicine Animals Nitric Oxide Donors Bone Resorption Mice Knockout Multidisciplinary biology Penicillamine Skull NF-kappa B Cell Differentiation Biological Sciences Coculture Techniques Nitric oxide synthase Endocrinology medicine.anatomical_structure chemistry Parathyroid Hormone biology.protein Bone marrow Nitric Oxide Synthase Interleukin-1 Protein Binding |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 97(14) |
| ISSN: | 0027-8424 |
| Popis: | Nitric oxide has been suggested to be involved in the regulation of bone turnover, especially in pathological conditions characterized by release of bone-resorbing cytokines. The cytokine IL-1 is thought to act as a mediator of periarticular bone loss and tissue damage in inflammatory diseases such as rheumatoid arthritis. IL-1 is a potent stimulator of both osteoclastic bone resorption and expression of inducible nitric oxide synthase (iNOS) in bone cells and other cell types. In this study, we investigated the role that the iNOS pathway plays in mediating the bone-resorbing effects of IL-1 by studying mice with targeted disruption of the iNOS gene. Studiesin vitroandin vivoshowed that iNOS-deficient mice exhibited profound defects of IL-1-induced osteoclastic bone resorption but responded normally to calciotropic hormones such as 1,25 dihydroxyvitamin D3 and parathyroid hormone. Immunohistochemical studies and electrophoretic mobility shift assays performed on bone marrow cocultures from iNOS-deficient mice showed abnormalities in IL-1-induced nuclear translocation of the p65 component of NFκB and in NFκB-DNA binding, which were reversed by treatment with the NO donorS-nitroso-acetyl penicillamine. These results show that the iNOS pathway is essential for IL-1-induced bone resorption and suggest that the effects of NO may be mediated by modulating IL-1-induced nuclear activation of NFκB in osteoclast precursors. |
| Databáze: | OpenAIRE |
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