title: Oxidized low-density lipoprotein promotes osteoblastic differentiation of valvular interstitial cells through RAGE/MAPK.
abstract: OBJECTIVE
  We have previously shown that oxidized low-density lipoprotein (oxLDL) promotes the osteogenic differentiation of valvular interstitial cells (VICs) by inducing endoplasmic reticulum (ER) stress. We also demonstrated the detrimental role of the receptor for advanced glycation end products (RAGE) activation and signaling in the development and progression of aortic valve (AV) calcification. Here, we test the hypothesis that oxLDL may induce the osteoblastic differentiation of VICs via RAGE.
  
  
  METHODS
  Cultured porcine aortic VICs were used in an in vitro model. The VICs were incubated with oxLDL for analysis, with and without RAGE siRNA.
  
  
  RESULTS
  We found that oxLDL markedly increased the expression of RAGE, induced high levels of proinflammatory cytokine production and promoted the osteoblastic differentiation and calcification of VICs. oxLDL also induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) MAPK. However, these effects were found to be markedly suppressed by siRNA silencing of RAGE.
  
  
  CONCLUSIONS
  Our data provide evidence that RAGE mediates oxLDL-induced activation of p38 and JNK MAPK and the osteogenic differentiation of VICs.
authors.affiliation: Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhejun
authors.initials: Z
authors.lastname: Cai
authors.forename: Nianguo
authors.initials: N
authors.lastname: Dong
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000166:cytology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D023421:Models, Animal; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D034741:RNA, Small Interfering; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C099252:oxidized low density lipoprotein; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases