Document Detail

Targeting Fas in osteoresorptive disorders.
MedLine Citation:
PMID:  20854180     Owner:  NLM     Status:  MEDLINE    
IMPORTANCE OF THE FIELD: Fas receptor is a mediator of the external apoptotic pathway in many cells and tissues. It is proposed that Fas receptor mediates osteoresorptive effects of estrogen deficiency and local/systemic inflammation.
AREAS COVERED IN THIS REVIEW: This review covers the past two decades of research on the expression and function of the Fas-Fas ligand system on bone cells, involvement in the pathogenesis of osteoresorption and potential therapeutic modulation.
WHAT THE READER WILL GAIN: We review the structure, biological function and intracellular signaling pathways of the Fas-Fas ligand system emphasizing the role of the non-apoptotic signaling pathways in bone cells, particularly osteoblast differentiation. We also present data on the in vitro expression and function of the Fas-Fas ligand system on osteoblast/osteoclast lineage cells, animal and human studies confirming its involvement in osteoresorptive disorders and potential therapeutic approaches to modulate its function.
TAKE HOME MESSAGE: Tissue specific therapeutic approaches need to be established to modify the Fas-Fas ligand system in osteoresorptive disorders as systemic targeting has many side effects. The most promising approach would be to target Fas signaling molecules coupled with osteoblast/osteoclast differentiation pathways, but a precise definition of these targets is still needed.
Natasa Kovacic; Danka Grcevic; Vedran Katavic; Ivan Kresimir Lukic; Ana Marusic
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Expert opinion on therapeutic targets     Volume:  14     ISSN:  1744-7631     ISO Abbreviation:  Expert Opin. Ther. Targets     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-03-09     Revised Date:  2011-07-27    
Medline Journal Info:
Nlm Unique ID:  101127833     Medline TA:  Expert Opin Ther Targets     Country:  England    
Other Details:
Languages:  eng     Pagination:  1121-34     Citation Subset:  IM    
University of Zagreb School of Medicine, Department of Anatomy, Zagreb, HR-10000, Croatia.
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MeSH Terms
Antigens, CD95 / antagonists & inhibitors*,  metabolism
Bone Resorption / genetics,  physiopathology*
Bone and Bones / physiology,  physiopathology
Cell Differentiation
Cell Lineage
Fas Ligand Protein / metabolism,  pharmacology,  therapeutic use*
Gene Expression
Molecular Targeted Therapy
Osteoblasts / cytology,  drug effects,  metabolism
Osteoclasts / cytology,  drug effects,  metabolism
Signal Transduction / drug effects
Grant Support
073828//Wellcome Trust; CRIGS 073828/Z/03/Z//Wellcome Trust
Reg. No./Substance:
0/Antigens, CD95; 0/Fas Ligand Protein

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