Nguyen Kirsten Q T, Olesen Ping, Ledet Thomas, Rasmussen Lars Melholt
Research Laboratory for Biochemical Pathology, Aarhus University Hospital, Aarhus, Denmark.
Endocrine. 2007 Aug;32(1):52-8. doi: 10.1007/s12020-007-9007-0. Epub 2007 Sep 29.
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.
骨相关蛋白骨保护素（OPG）可能参与血管钙化的发展，尤其是在糖尿病中，在糖尿病患者的动脉壁中已发现其含量增加。实验研究表明，转化生长因子-β（TGF-β）超家族成员参与人血管平滑肌细胞（HVSMC）向成骨样细胞的转化。在本研究中，我们评估了骨形态发生蛋白-2（BMP-2）、骨形态发生蛋白-7（BMP-7）和转化生长因子-β1（TGF-β1）对HVSMC中OPG及其配体核因子κB受体活化因子配体（RANKL）和肿瘤坏死因子相关凋亡诱导配体（TRAIL）分泌及mRNA表达的影响。所有这三种生长因子均显著降低OPG蛋白的产生；这些结果与OPG mRNA表达降低相平行。TRAIL mRNA水平也降低。用TGF-β1处理时RANKL mRNA表达下降，但两种骨形态发生蛋白均使其增加。TGF-β超家族成员，即TGF-β1、BMP-2和BMP-7对OPG及其配体产生影响，表明这些肽可能参与血管钙化的发展。然而，这些肽对OPG的下调并不表明这些因子直接参与糖尿病中OPG的积累。
