Document Detail


Causative agents of osteomyelitis induce death domain-containing TNF-related apoptosis-inducing ligand receptor expression on osteoblasts.
MedLine Citation:
PMID:  21130908     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Bacteria and their products are potent inducers of bone destruction. While inflammatory damage during conditions such as osteomyelitis is associated with increased formation and activity of bone-resorbing osteoclasts, it is likely that bone loss also results from the elimination of the cells responsible for matrix deposition. Consistent with this notion, we have previously demonstrated that bone-forming osteoblasts undergo apoptosis following bacterial challenge and that this cell death is due, at least in part, to the actions of TNF-related apoptosis-inducing ligand (TRAIL). In the present study, we demonstrate that primary osteoblasts constitutively express death domain containing TRAIL receptors. Importantly, we show that cell surface expression of the death-inducing receptors DR4 and DR5 on murine and human osteoblasts is restricted to cells infected with the principle causative agents of osteomyelitis, Staphylococcus aureus and Salmonella. In addition, we show that the robust constitutive production by osteoblasts of the decoy TRAIL receptor, OPG, is inhibited following bacterial infection. Finally, we report that while exogenous administration of TRAIL fails to activate apoptosis signaling pathways in uninfected osteoblasts, acute bacterial exposure sensitizes these cells to this ligand. Based upon these findings we suggest a model in which bacterially challenged osteoblasts express TRAIL while concomitantly decreasing the production of the decoy receptor OPG and upregulating cell surface death receptor expression. Such an increase in TRAIL bioavailability and induced sensitivity of infected osteoblasts to this ligand would result in apoptotic cell death of this bone-forming population, providing an additional mechanism underlying inflammatory bone loss during diseases such as osteomyelitis.
Authors:
Amy B Young; Ian D Cooley; Vinita S Chauhan; Ian Marriott
Related Documents :
15814658 - Myc down-regulation sensitizes melanoma cells to radiotherapy by inhibiting mlh1 and ms...
21412788 - Translocase of outer mitochondrial membrane 70 expression is induced by hepatitis c vir...
21459928 - Apoptosis of regulatory t lymphocytes is increased in chronic inflammatory bowel diseas...
8810318 - Double-stranded rna-dependent protein kinase mediates c-myc suppression induced by type...
23535518 - Phenylmethimazole suppresses dsrna-induced cytotoxicity and inflammatory cytokines in m...
24081898 - Il-6 trans-signaling enhances ccl20 production from il-1β-stimulated human periodontal...
Publication Detail:
Type:  Journal Article     Date:  2010-12-03
Journal Detail:
Title:  Bone     Volume:  48     ISSN:  1873-2763     ISO Abbreviation:  Bone     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8504048     Medline TA:  Bone     Country:  United States    
Other Details:
Languages:  eng     Pagination:  857-63     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Proteomic analysis of salicylic acid induced resistance to Mungbean Yellow Mosaic India Virus in Vig...
Next Document:  Proximal femur structural geometry changes during and following lactation.