Document Detail


Oxidized low density lipoprotein decreases Rankl-induced differentiation of osteoclasts by inhibition of Rankl signaling.
MedLine Citation:
PMID:  19725047     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of OxLDL in the generation and progression of atherosclerosis is well admitted. In addition, it is well known that atherosclerosis is often accompanied by perturbations in bone remodeling, resulting in osteoporosis. In the current studies, the effect of Cu(2+)-oxidized LDL (OxLDL) on RANKL-induced RAW264.7 mouse monocytes-macrophages differentiation to osteoclasts and on RANKL signaling pathway was investigated. OxLDL, within the range of 10-50 microg protein/ml, prevented RANKL-induced generation of multinucleated osteoclast-like cells and RANKL-induced tartrate resistant acid phosphatase (TRAP) activity. OxLDL also prevented the RANKL-induced phosphorylation of ERK, p38 and JNK kinases, together with the RANKL-induced DNA binding activities of NFkappaB and NFAT transcription factors. Concomitantly, OxLDL enhanced RANKL-induced generation of reactive oxygen species in a dose-dependent manner. The antioxidant glutathione (GSH) prevented whereas the prooxidant compound buthionine-sulfoximine (BSO) enhanced the effect of OxLDL on RANKL-induced oxidative stress and RANKL-induced differentiation. Finally, OxLDL also prevented RANKL-induced TRAP activity and RANKL-induced bone resorbing activity of human peripheral blood mononuclear cells. These results demonstrate that OxLDL, by generation of an intracellular oxidative stress, prevents the differentiation of osteoclasts by inhibition of RANKL signaling pathway. This might be related to the fact that atherosclerosis is accompanied by perturbations in bone and vascular remodeling, leading to osteoporosis and vascular calcification.
Authors:
Cécile Mazière; Loïc Louvet; Cathy Gomila; Said Kamel; Ziad Massy; Jean-Claude Mazière
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  221     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-10-01     Completed Date:  2009-11-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  572-8     Citation Subset:  IM    
Affiliation:
INSERM ERI-12, Amiens, France. maziere.cecile@chu-amiens.fr
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MeSH Terms
Descriptor/Qualifier:
Acid Phosphatase / metabolism
Animals
Bone Resorption / pathology
Buthionine Sulfoximine / pharmacology
Cell Differentiation / drug effects*,  physiology
Cell Line, Tumor
Extracellular Signal-Regulated MAP Kinases / metabolism
Glutathione / pharmacology
Humans
Isoenzymes / metabolism
Lipoproteins, LDL / pharmacology*
MAP Kinase Kinase 4 / metabolism
Macrophages / cytology,  drug effects,  metabolism
Mice
Monocytes / cytology,  drug effects,  metabolism
NF-kappa B / metabolism
NFATC Transcription Factors / metabolism
Osteoclasts / cytology*,  metabolism
Phosphorylation / drug effects
RANK Ligand / pharmacology*
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*,  physiology
p38 Mitogen-Activated Protein Kinases / metabolism
Chemical
Reg. No./Substance:
0/Isoenzymes; 0/Lipoproteins, LDL; 0/NF-kappa B; 0/NFATC Transcription Factors; 0/RANK Ligand; 0/Reactive Oxygen Species; 0/TNFSF11 protein, human; 0/Tnfsf11 protein, mouse; 0/oxidized low density lipoprotein; 5072-26-4/Buthionine Sulfoximine; 70-18-8/Glutathione; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases; EC 2.7.12.2/MAP Kinase Kinase 4; EC 3.1.3.-/tartrate-resistant acid phosphatase; EC 3.1.3.2/Acid Phosphatase

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


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