Document Detail


Fas/CD95 is associated with glucocorticoid-induced osteocyte apoptosis.
MedLine Citation:
PMID:  15454340     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
G Kogianni; V Mann; F Ebetino; M Nuttall; P Nijweide; H Simpson; B Noble
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Life sciences     Volume:  75     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-29     Completed Date:  2004-12-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2879-95     Citation Subset:  IM    
Affiliation:
University of Edinburgh, Musculoskeletal Research Unit, Edinburgh, UK.
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MeSH Terms
Descriptor/Qualifier:
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:
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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