Bone morphogenetic proteins regulate osteoprotegerin and its ligands in human vascular smooth muscle cells.
The bone-related protein osteoprotegerin (OPG) may be involved in the development of vascular calcifications, especially in diabetes, where it has been found in increased amounts in the arterial wall. Experimental studies suggest that members of the TGF-superfamily are involved in the transformation of human vascular smooth muscle cells (HVSMC) to osteoblast-like cells. In this study, we evaluated the effect of BMP-2, BMP-7 and transforming growth factor beta (TGF-beta1) on the secretion and mRNA expression of OPG and its ligands receptor activator of nuclear factor-kappabeta ligand (RANKL) and TNF-related apoptosis-inducing ligand (TRAIL) in HVSMC. All three growth factors decreased OPG protein production significantly; these results were paralleled by reduced OPG mRNA expression. TRAIL mRNA levels were also decreased. RANKL mRNA expression declined when treated with TGF-beta1 but were increased by both BMPs. Members of the TGF-superfamily, i.e. TGF-beta1, BMP-2 and BMP-7 exert effects on OPG and its ligands, indicating that these peptides may be involved in the development of vascular calcifications. The downregulation of OPG by these peptides does, however, not suggest that these factors are directly involved in OPG accumulation in diabetes.
Nguyen
Kirsten Q T
KQ
Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Aarhus, Denmark.
Olesen
Ping
P
Ledet
Thomas
T
Rasmussen
Lars Melholt
LM
D000199:Actins / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002114:Calcinosis / Q000378:metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D053244:Osteoprotegerin / Q000096:biosynthesis*; D053245:RANK Ligand / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000199:Actins; D019485:Bone Morphogenetic Proteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D016212:Transforming Growth Factor beta