Schweighofer N, Aigelsreiter A, Trummer O, Graf-Rechberger M, Hacker N, Kniepeiss D, Wagner D, Stiegler P, Trummer C, Pieber T, Obermayer-Pietsch B, Müller H
Department of Internal Medicine, Divison of Endocrinology and Diabetology, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036 Graz, Austria.
Bone. 2016 Jul;88:31-38. doi: 10.1016/j.bone.2016.04.016. Epub 2016 Apr 20.
Calcification is not only physiologically present in bone but is a main pathophysiological process in vasculature, favouring cardiovascular diseases. Our aim was to investigate changes in the expression of calcification regulators during vascular calcification in bone and vasculature. Levels of gene expression of osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), osteopontin (OPN), matrix gla protein (MGP), bone sialoprotein (BSP), SMAD6, and runt-related transcription factor 2 (RUNX2) were determined in bone, aorta, and external iliac artery tissue samples of transplant donors. Histological stages of atherosclerosis (AS) in vessels are defined as "no changes", "intima thickening", or "intima calcification". Patients' bone samples were subgrouped accordingly. We demonstrate that in vessels BSP and OPN expression significantly increased during intima thickening and decreased during intima calcification, whereas the expression of regulators of calcification did not significantly change in bone during intima thickening and intima calcification. At the stage of intima thickening, MGP, OPG, and SMAD6 expression and at stage of intima calcification only MGP expression was lower in bone than in vessel. The expression of BSP and RANKL was regulated in opposite ways in bone and vessels, whereas the expression of MGP, OC, RUNX2, and OPN was regulated in a tissue-specific manner. Our study is the first direct comparison of gene expression changes during AS progression in bone and vessels. Our results indicate that changes in the expression of regulators of calcification in the vessel wall as well as in bone occur early in the calcification process, even prior to deposition of calcium/phosphate precipitation.
钙化不仅在生理状态下存在于骨骼中，也是血管系统中的一个主要病理生理过程，会引发心血管疾病。我们的目的是研究骨骼和血管系统发生血管钙化时钙化调节因子表达的变化。在移植供体的骨骼、主动脉和髂外动脉组织样本中，测定了骨保护素（OPG）、核因子κB受体活化因子配体（RANKL）、骨桥蛋白（OPN）、基质γ-羧基谷氨酸蛋白（MGP）、骨唾液酸蛋白（BSP）、SMAD6和 runt相关转录因子2（RUNX2）的基因表达水平。血管中动脉粥样硬化（AS）的组织学阶段被定义为“无变化”、“内膜增厚”或“内膜钙化”。患者的骨样本据此进行分组。我们证明，在血管中，BSP和OPN的表达在内膜增厚期间显著增加，而在内膜钙化期间降低，而在骨骼中，钙化调节因子的表达在内膜增厚和内膜钙化期间没有显著变化。在内膜增厚阶段，骨骼中的MGP、OPG和SMAD6表达以及在内膜钙化阶段仅MGP表达低于血管中的表达。BSP和RANKL的表达在骨骼和血管中以相反的方式受到调节，而MGP、OC、RUNX2和OPN的表达则以组织特异性方式受到调节。我们的研究是首次对骨骼和血管中AS进展过程中的基因表达变化进行直接比较。我们的结果表明，血管壁以及骨骼中钙化调节因子表达的变化在钙化过程的早期就会发生，甚至在钙/磷酸盐沉淀沉积之前。
