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https://hdl.handle.net/2440/6659
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Type: | Journal article |
Title: | Human osteoblasts are resistant to Apo2L/TRAIL-mediated apoptosis |
Author: | Atkins, G. Bouralexis, S. Evdokiou, A. Hay, S. Labrinidis, A. Zannettino, A. Haynes, D. Findlay, D. |
Citation: | Bone, 2002; 31(4):448-456 |
Publisher: | Elsevier Science Inc |
Issue Date: | 2002 |
ISSN: | 8756-3282 1873-2763 |
Statement of Responsibility: | G. J. Atkins, S. Bouralexis, A. Evdokiou, S. Hay, A. Labrinidis, A. C. W. Zannettino, D. R. Haynes and D. M. Findlay |
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. |
Keywords: | Human osteoblasts Apo2L/TRAIL Receptors Apoptosis Caspase Chemotherapy |
Description: | Copyright © 2002 Elsevier Science Inc. All rights reserved. |
DOI: | 10.1016/S8756-3282(02)00858-X |
Description (link): | http://www.elsevier.com/wps/find/journaldescription.cws_home/525233/description#description |
Published version: | http://dx.doi.org/10.1016/s8756-3282(02)00858-x |
Appears in Collections: | Aurora harvest 5 Orthopaedics and Trauma publications |
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