Expression of bone-regulating factors osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) in heterotopic vascular ossification
Expression of bone-regulating factors osteoprotegerin (OPG) and receptor activator of NF-κB ligand (RANKL) in heterotopic vascular ossification
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DOI：
10.1160/th05-06-1335
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发表时间：
2005-12-01
影响因子：
6.7
通讯作者：
Schoppet, M
中科院分区：
文献类型：
--
作者：
Al-Fakhri, N;Hofbauer, LC;Schoppet, M
血管钙化的特征是骨相关基质蛋白的表达和血管壁中骨样结构的存在 (1)。最近，护骨素 (OPG)、NF-κB 配体受体激活剂 (RANKL) 和 NF-κB 受体激活剂 (RANK) 已成为骨代谢的重要调节剂 (2)，并且还与血管钙化有关 (3)。 OPG 充当 RANKL 和肿瘤坏死因子相关凋亡诱导配体 (TRAIL) 的诱饵受体，TRAIL 是易感细胞中的凋亡诱导剂 (4)。值得注意的是，OPG 缺陷小鼠表现出严重骨质疏松和大动脉内侧钙化的表型 (5)。我们假设异位血管骨化中存在 RANKL/OPG/TRAIL 系统的失衡。一名 59 岁男性，患有主动脉冠状动脉搭桥手术移植的冠状动脉疾病、糖尿病并发终末期肾病（血液透析 3 年）、继发性甲状旁腺功能亢进、动脉高血压、高脂蛋白血症和肥胖，因晚期外周动脉疾病和缺血性足坏疽入院。双下肢必须在六个月内截肢。术前一年，血清甲状旁腺激素和磷酸盐水平分别升高至7.7 pmol/L（正常：1.0-5.5 pmol/L）和1.9 mmol/L（正常：0.8-1.6 mmol/L），血清钙水平处于正常上限范围内，为2.6 mmol/L（正常：2.0-2.6 mmol/L）。常规检查动脉钙化明显X 射线（图 1A）。使用的组织样本是废料，并根据机构指南进行分析。从股动脉、腘动脉和胫动脉获取标本，立即处理，并用 4% 甲醛/PBS 固定 12 小时。使用 10% EDTA Tris 缓冲溶液或酸脱钙（2.5% 盐酸、9.5% 甲酸）对一半标本进行脱钙，并石蜡包埋。脱蜡和复水后，所有标本的连续切片进行苏木精和伊红染色，
Vascular calcification is characterized by expression of bone-related matrix proteins and the presence of bonelikestructuresinthevesselwall (1). Recently, osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL), and receptor activator of NF-κB (RANK) have emerged as essential regulators of bone metabolism (2) and have also been implicated in vascular calcification (3). OPG acts as a decoy receptor for RANKL and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an inducer of apoptosis in susceptible cells (4). Of note, OPG-deficient mice display a phenotype of severe osteoporosis and medial calcification of great arteries (5). We hypothesized that a dysbalance of the RANKL/OPG/TRAIL system is present in heterotopic vascular ossification. A 59-year-old man with coronary artery disease grafted by aorto-coronary bypass surgery, diabetes mellitus complicated by end-stage nephropathy (3 years on hemodialysis), secondary hyperparathyroidism, arterial hypertension, hyperlipoproteinemia, and obesity was admitted with advanced peripheral arterial disease and ischemic pedal gangrene. Both lower limbs had to be amputated within an interval of 6 months. One year before surgery, serum levels of parathyroid hormone and phosphate had been elevated at 7.7 pmol/L (normal: 1.0–5.5 pmol/L) and 1.9 mmol/L (normal: 0.8–1.6 mmol/L), respectively, calcium serum levels were within the upper normal range at 2.6 mmol/L (normal: 2.0–2.6 mmol/L).Arterial calcification was apparent on conventional X-ray (Fig. 1A). Tissue samples used were waste material and were analyzed in accordance with institutional guidelines. Specimens were obtained from the femoral, popliteal, and tibial arteries, processed immediately, and fixed with 4% formaldehyde/PBS for 12 h. Half of the specimens were decalcified, using either 10% EDTA Tris-buffered solution or acid decalcification (2.5% hydrochloric acid, 9.5% formic acid), and paraffin-embedded. After deparaffinization and rehydration, serial sections of all specimens were subjected to hematoxylin and eosin staining,