| Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis. | |
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MedLine Citation:
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PMID: 15454340 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Prolonged use of glucocorticoids is associated with decreased bone formation, increased resorption and osteonecrosis, through direct and indirect effects on the activity and viability of bone effector cells, osteoblasts and osteoclasts, and osteocytes. This study has investigated molecular pathways implicated in Dexamethasone-induced apoptosis of osteocytes, using a cell line and primary chicken cells. MLO-Y4 osteocytes were pre-treated with several bisphosphonates representing a range of anti-resorptive activities and conformation/structure relationships, and were subsequently challenged with Dexamethasone. Apoptotic cells were detected at various times after treatment using morphological and biochemical criteria. Dex was shown to induce apoptosis associated with the Fas/CD95 death receptor and in a caspase 8 dependent manner. The apoptotic response was inhibited by all variants of the BP molecules, including those with reduced anti-resorptive activity, indicating that Dex-induced apoptosis is independent of anti-osteoclastic activity. Dex-induced apoptosis was associated with a transient increase in phosphorylated ERK 1/2 and was blocked by the ERK inhibitor UO126. In addition, both UO126 and BPs decreased localization of Fas to the cell membrane. ERK activation by PMA did not induce death or Fas upregulation, suggesting that Fas may be important for the induction of apoptosis and the existence of an additional factor activated by Dex which enables the cooperation between the Dex-activated ERK and Fas pathways, during apoptosis of osteocytes. Furthermore, upregulation of death and Fas was not accompanied by upregulation of FasL, pointing to the possible existence of FasL-independent Fas-associated death in these cells. |
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Authors:
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G Kogianni; V Mann; F Ebetino; M Nuttall; P Nijweide; H Simpson; B Noble |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Life sciences Volume: 75 ISSN: 0024-3205 ISO Abbreviation: Life Sci. Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-29 Completed Date: 2004-12-14 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0375521 Medline TA: Life Sci Country: England |
Other Details:
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Languages: eng Pagination: 2879-95 Citation Subset: IM |
Affiliation:
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University of Edinburgh, Musculoskeletal Research Unit, Edinburgh, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Antigens, CD95 / metabolism* Apoptosis / drug effects* Blotting, Western Butadienes / pharmacology Cell Line Chickens DNA Primers Dexamethasone / pharmacology* Immunohistochemistry Immunoprecipitation Mice Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors, metabolism Nitriles / pharmacology Osteocytes / drug effects* Phosphonic Acids / pharmacology* RNA / genetics Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antigens, CD95; 0/Butadienes; 0/DNA Primers; 0/Nitriles; 0/Phosphonic Acids; 0/U 0126; 50-02-2/Dexamethasone; 63231-63-0/RNA; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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