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https://hdl.handle.net/2440/6659
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dc.contributor.author | Atkins, G. | - |
dc.contributor.author | Bouralexis, S. | - |
dc.contributor.author | Evdokiou, A. | - |
dc.contributor.author | Hay, S. | - |
dc.contributor.author | Labrinidis, A. | - |
dc.contributor.author | Zannettino, A. | - |
dc.contributor.author | Haynes, D. | - |
dc.contributor.author | Findlay, D. | - |
dc.date.issued | 2002 | - |
dc.identifier.citation | Bone, 2002; 31(4):448-456 | - |
dc.identifier.issn | 8756-3282 | - |
dc.identifier.issn | 1873-2763 | - |
dc.identifier.uri | http://hdl.handle.net/2440/6659 | - |
dc.description | Copyright © 2002 Elsevier Science Inc. All rights reserved. | - |
dc.description.abstract | Apo2 ligand (Apo2L/TRAIL) is a member of the tumor necrosis factor (TNF) cytokine family. Apo2L/TRAIL can selectively induce programmed cell death in transformed cells, although its wide tissue distribution suggests potential physiological roles. We have investigated the expression, in human osteoblast-like cells (NHBC), of Apo2L/TRAIL and the known Apo2L/TRAIL death receptors, DR4 and DR5, and the Apo2L/TRAIL decoy receptors, DcR-1, DcR-2, and osteoprotegerin (OPG). NHBC expressed abundant mRNA corresponding to each of these molecular species. Immunofluorescence staining demonstrated that Apo2L/TRAIL protein was abundant within the cytoplasm of NHBC and OPG was strongly expressed at the cell surface. DR5 and DcR-2 were present in the cell membrane and cytoplasm and DcR-1 was confined to the nucleus. DR4 staining was weak. Neither Apo2L/TRAIL alone, nor in combination with chemotherapeutic agents of clinical relevance to treatment of osteogenic sarcoma, induced cell death in NHBC, as assessed morphologically and by activation of caspase-3. In contrast, the human osteogenic sarcoma cell lines, BTK-143 and G-292, were sensitive to exogenous Apo2L/TRAIL alone, and to the combined effect of Apo2L/TRAIL/cisplatin and Apo2L/TRAIL/doxorubicin treatments, respectively. In NHBC, we observed strong associations between the levels of mRNA corresponding to the pro-apoptotic molecules, Apo2L/TRAIL, DR4, and DR5, and those corresponding to pro-survival molecules, DcR-1, DcR-2, OPG, and FLIP, suggesting that the balance between pro-survival and pro-apoptotic molecules is a mechanism by which NHBC can resist Apo2L/TRAIL-mediated apoptosis. In contrast, osteogenic sarcoma cells had low or absent levels of DcR-1 and DcR-2. These results provide a foundation to explore the role of Apo2L/TRAIL in osteoblast physiology. In addition, they predict that therapeutic use of recombinant Apo2L/TRAIL, in combination with chemotherapeutic agents to treat skeletal malignancies, would have limited toxic effects on normal osteoblastic cells. | - |
dc.description.statementofresponsibility | G. J. Atkins, S. Bouralexis, A. Evdokiou, S. Hay, A. Labrinidis, A. C. W. Zannettino, D. R. Haynes and D. M. Findlay | - |
dc.description.uri | http://www.elsevier.com/wps/find/journaldescription.cws_home/525233/description#description | - |
dc.language.iso | en | - |
dc.publisher | Elsevier Science Inc | - |
dc.source.uri | http://dx.doi.org/10.1016/s8756-3282(02)00858-x | - |
dc.subject | Human osteoblasts | - |
dc.subject | Apo2L/TRAIL | - |
dc.subject | Receptors | - |
dc.subject | Apoptosis | - |
dc.subject | Caspase | - |
dc.subject | Chemotherapy | - |
dc.title | Human osteoblasts are resistant to Apo2L/TRAIL-mediated apoptosis | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1016/S8756-3282(02)00858-X | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Atkins, G. [0000-0002-3123-9861] | - |
dc.identifier.orcid | Evdokiou, A. [0000-0001-8321-9806] | - |
dc.identifier.orcid | Zannettino, A. [0000-0002-6646-6167] | - |
Appears in Collections: | Aurora harvest 5 Orthopaedics and Trauma publications |
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