PDGF induces osteoprotegerin expression in vascular smooth muscle cells by multiple signal pathways.
Osteoprotegerin (OPG) is a key regulator of osteoclastogenesis. Recent reports suggest that OPG may function as a protector of arterial calcification and survival of endothelial cells. However, the role and expression of OPG in vascular wall is unclear. Here we report that OPG was highly expressed in vascular smooth muscle cells (VSMC) but not in endothelial cells. Platelet-derived growth factor (PDGF), basic fibroblast growth factor, angiotensin II, tumor necrosis factor alpha and interleukin-1beta upregulated OPG expression in VSMC. Moreover, inhibition of phosphatidylinositol 3-kinase/Akt or P38-signal pathway abrogated PDGF-induced OPG expression. Our results suggest that OPG may be an important determinant of vascular homeostasis.
Zhang
Jifeng
J
Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310, USA.
Fu
Mingui
M
Myles
David
D
Zhu
Xiaojun
X
Du
Jie
J
Cao
Xu
X
Chen
Yuqing E
YE
D000804:Angiotensin II / Q000494:pharmacology; D000077214:Becaplermin; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D008024:Ligands; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D053244:Osteoprotegerin; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases
D000804:Angiotensin II; D000077214:Becaplermin; D002352:Carrier Proteins; D016222:Fibroblast Growth Factor 2; D006023:Glycoproteins; D007375:Interleukin-1; D008024:Ligands; D008562:Membrane Glycoproteins; D020928:Mitogen-Activated Protein Kinases; D053244:Osteoprotegerin; D019869:Phosphatidylinositol 3-Kinases; D010982:Platelet-Derived Growth Factor; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D020574:Proto-Oncogene Proteins c-sis; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C494918:AKT1 protein, human