title: Oxidized low density lipoprotein enhanced RANKL expression in human osteoblast-like cells. Involvement of ERK, NFkappaB and NFAT.
abstract: BACKGROUND
  Receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand/osteoprotegerin ratio is of crucial importance in osteoclast differentiation and thus in bone dysregulation diseases.
  
  
  METHODS
  Receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand and osteoprotegerin were determined under oxidized low density lipoprotein treatment of human osteoblast-like cells. The involvement of oxidative stress, of the extracellular signal regulated kinase and of the transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells and nuclear factor of activated T cells was demonstrated.
  
  
  RESULTS
  Cu(2+)-oxidized low density lipoprotein increased cell-associated and extracellular receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand levels whereas osteoprotegerin levels were not affected. The increase in receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand was parallel to the generation of reactive oxygen species provoked by Cu(2+)-oxidized low density lipoprotein. The lipid extract of Cu(2+)-oxidized low density lipoprotein, together with other forms of oxidized low density lipoproteins such as smooth muscle cell-oxidized low density lipoprotein and myeloperoxidase-oxidized low density lipoprotein, also induced an increase in reactive oxygen species and cell-associated receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand. The effect of Cu(2+)-oxidized low density lipoprotein was prevented by the antioxidant vitamin E, and mimicked by the prooxidant compounds hydrogen peroxide and buthionine sulfoximine. Inhibitors of mitogen activated protein kinase/extracellular signal regulated kinase (PD 98059), nuclear factor kappa-light-chain-enhancer of activated B cells (Ro 106-9920) and nuclear factor of activated T cells (Vivit) reduced the effect of Cu(2+)-oxidized low density lipoprotein on receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cell ligand expression. Cu(2+)-oxidized low density lipoprotein signaling was also reduced by vitamin E.
  
  
  CONCLUSIONS
  This work describes a new molecular mechanism and elucidates the signaling pathway whereby oxidized low density lipoprotein, by means of its lipid moiety, can modulate the crosstalk between osteoblasts/osteoclasts and bone remodeling, leading to an eventual risk of osteoporosis.
authors.affiliation: South Central Hospital University, Amiens, France. maziere.cecile@chu-amiens.fr
authors.forename: Cécile
authors.initials: C
authors.lastname: Mazière
authors.forename: Valéry
authors.initials: V
authors.lastname: Salle
authors.forename: Cathy
authors.initials: C
authors.lastname: Gomila
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Mazière
mesh_terms: D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C505688:TNFSF11 protein, human; C099252:oxidized low density lipoprotein; D009195:Peroxidase; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: BSO; Cu(2+)-oxidized low density lipoprotein; CuLDL; H(2)O(2); MPO-LDL; NFAT; OPG; Osteoporosis; OxLDL; Oxidative stress; Oxidized LDL; RANKL; ROS; SMC-LDL; buthionine sulfoximine; hydrogen peroxide; myeloperoxidase-oxidized LDL; nLDL; native LDL; nuclear factor of activated T cells; osteoprotegerin; oxidized LDL; reactive oxygen species; receptor activator of NFkappaB ligand; smooth muscle cell-oxidized LDL