Lanthanum suppresses osteoblastic differentiation via pertussis toxin-sensitive G protein signaling in rat vascular smooth muscle cells.
A major cellular event in vascular calcification is the phenotypic transformation of vascular smooth muscle cells (VSMCs) into osteoblast-like cells. After demonstrating that lanthanum chloride (LaCl(3)) suppresses hydrogen peroxide-enhanced calcification in rat calcifying vascular cells (CVCs), here we report its effect on the osteoblastic differentiation of rat VSMCs, a process leading to the formation of CVCs. Cells were isolated from aortic media of male SD rats, and passages between three and eight were cultured in Dulbeccol's Modified Eagle's Medium (DMEM) containing 10% fetal bovine serum (FBS) and 10 mM beta-glycerophosphate (beta-GP) in the presence or absence of LaCl(3). Exposure of cells to LaCl(3) suppressed the beta-GP-induced elevations in calcium deposition, alkaline phosphatase (ALP) activity, and Cbfa1/Runx2 expression, as well as the concomitant loss of SM alpha-actin. Furthermore, LaCl(3) activated the phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), and the blockage of either pathway with a specific inhibitor abolished the effects of LaCl(3). In addition, pretreatment of the cells with pertussis toxin (PTx), an inhibitor of G protein-mediated signaling pathway, repealed all the changes induced by LaCl(3). These findings demonstrate that LaCl(3) suppresses the beta-GP-induced osteoblastic differentiation and calcification in rat VSMCs, and its effect is mediated by the activation of both ERK and JNK MAPK pathways via PTx-sensitive G proteins.
Shi
Yan-Ling
YL
Department of Chemical Biology, Capital Medical University School of Pharmaceutical Sciences, 10 Xitoutiao, You An Men, Beijing 100069, PR China.
Wang
Li-Wen
LW
Huang
Jian
J
Gou
Bao-Di
BD
Zhang
Tian-Lan
TL
Wang
Kui
K
D000199:Actins / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002113:Calcification, Physiologic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D005994:Glycerophosphates / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007811:Lanthanum / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology*; D051381:Rats; D017540:Tunica Media
D000199:Actins; D050659:Core Binding Factor Alpha 1 Subunit; D005994:Glycerophosphates; C028521:lanthanum chloride; D007811:Lanthanum; D037342:Pertussis Toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase; D019204:GTP-Binding Proteins; D002118:Calcium