Bisphosphonates induce apoptosis in mouse macrophage-like cells in vitro by a nitric oxide-independent mechanism
| Autor: | F P Coxon, Roslin Russell, J. Lawry, S. Suri, Michael J. Rogers, K. M. Chilton, M. O. Smith |
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| Rok vydání: | 1996 |
| Předmět: |
medicine.medical_specialty
Programmed cell death Necrosis Endocrinology Diabetes and Metabolism medicine.medical_treatment Pamidronate Apoptosis Bone Marrow Cells DNA Fragmentation urologic and male genital diseases Nitric Oxide Bone resorption Nitric oxide chemistry.chemical_compound Mice Osteoclast Bone Marrow Internal medicine medicine Animals Orthopedics and Sports Medicine Bone Resorption Ibandronic Acid Cells Cultured Cell Nucleus Alendronate Diphosphonates Macrophages DNA Bisphosphonate medicine.anatomical_structure Endocrinology chemistry Mechanism of action Protein Biosynthesis Cancer research Electrophoresis Polyacrylamide Gel medicine.symptom hormones hormone substitutes and hormone antagonists Cell Division |
| Zdroj: | Scopus-Elsevier |
| ISSN: | 0884-0431 |
| Popis: | Bisphosphonates (BPs) are an important class of antiresorptive drugs used in the treatment of bone diseases, including osteoporosis. Although their mechanism of action has not been identified at the molecular level, there is substantial evidence that BPs can have a direct effect on osteoclasts by mechanisms that may lead to osteoclast cell death by apoptosis. BPs can also inhibit proliferation and cause cell death in macrophages in vitro. We have now shown that the toxic effect of BPs on macrophages is also due to the induction of apoptotic, rather than necrotic, cell death. Morphological and biochemical features that are definitive of apoptosis (chromatin condensation, nuclear fragmentation, and endonuclease-mediated internucleosomal cleavage of DNA) could be identified in mouse macrophage-like J774 and RAW264 cells, following treatment with 100 microM pamidronate, alendronate, and ibandronate for 24 h or more. Clodronate was much less potent, even at 2000 microM, while 2000 microM etidronate did not cause apoptosis. Apoptosis was not due to increased synthesis of nitric oxide and could not be prevented by inhibitors of nitric oxide synthases. Since macrophages, like osteoclasts, are particularly susceptible to BPs, these observations support the recent suggestion that the mechanism by which BPs inhibit bone resorption may involve osteoclast apoptosis. Furthermore, the macrophage-like cell lines used in this study may be a convenient model with which to identify the molecular mechanisms by which BPs promote apoptosis in osteoclasts. Induction of macrophage apoptosis by BPs in vivo may also account, at least in part, for the anti-inflammatory properties of BPs as well as the ability of BPs to cause an acute phase response. |
| Databáze: | OpenAIRE |
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