Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal-regulated protein kinase 1/2 and nuclear factor-κB signaling pathways
Parathyroid hormone promotes osteoblastic differentiation of endothelial cells via the extracellular signal-regulated protein kinase 1/2 and nuclear factor-κB signaling pathways
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DOI：
10.3892/etm.2017.5545
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发表时间：
2018-02-01
影响因子：
2.7
通讯作者：
Zong, Gang-Jun
中科院分区：
文献类型：
--
作者：
Cheng, Zhi-Yuan;Ye, Ting;Zong, Gang-Jun
血管钙化（VC）发生在慢性肾脏病（CKD）患者中，并导致心血管功能障碍和死亡率。甲状旁腺激素（PTH）是VC的重要调节因子。高PTH血清水平构成CKD患者的主要危险因素。然而，PTH对内皮细胞向成骨细胞分化的影响及其机制尚未完全阐明。在本研究中，使用体外钙化模型研究PTH在VC中的作用。内皮细胞用PTH在毫微微至皮摩尔范围内刺激。通过蛋白质印迹分析和ELISA测定，成骨细胞分化，如BMP 2标记所示，在1 × 10（-10）mmol/l PTH时发生最大效应。结果表明，PTH促进内皮细胞的成骨分化，如骨形态发生蛋白（BMP）2和BMP 4的表达增加所证明的。此外，Western blot分析显示PTH激活了细胞外信号调节蛋白激酶（Erk）1/2和核因子（NF）-κ B B信号通路。然而，逆转录-定量聚合酶链反应表明，Erk 1/2和NF-κ B B特异性抑制剂消除了PTH治疗对BMP 2、BMP 4、ALP和RUNX 2表达的影响。这些结果表明，PTH通过Erk 1/2和NF-κ B信号通路促进内皮细胞的成骨分化，这表明PTH在促进VC中的潜在作用。这些发现提供了一个深入了解PTH和心血管疾病之间的关联。
Vascular calcification (VC) occurs in patients with chronic kidney disease (CKD) and contributes to cardiovascular dysfunction and mortality. Parathyroid hormone (PTH) is a crucial regulator of VC. High PTH serum levels constitute as a major risk factor for patients with CKD. However, the effect and mechanism of PTH on osteoblastic differentiation in endothelial cells have not been fully elucidated. In the present study, the role of PTH in VC was investigated using an in vitro calcification model. Endothelial cells were stimulated with PTH in the femto- to picomolar range. As determined by western blot analysis and ELISA, osteoblastic differentiation, as indicated by the BMP2 marker, occurred with maximum effect at 1x10(-10) mmol/l PTH. The results indicate that PTH promotes osteoblastic differentiation of endothelial cells, as demonstrated by the increased expression of bone morphogenetic protein (BMP) 2 and BMP4. In addition, western blot analysis revealed that PTH activated the extracellular signal-regulated protein kinase (Erk)1/2 and nuclear factor (NF)-kappa B signaling pathways. However, reverse transcription-quantitative polymerase chain reaction demonstrated that inhibitors specific to Erk1/2 and NF-kappa B eradicated the effect of PTH treatment on BMP2, BMP4, ALP and RUNX2 expression. These results demonstrate that PTH promotes the osteoblastic differentiation of endothelial cells via the Erk1/2 and NF-kappa B signaling pathways, which suggests a potential role of PTH in the promotion of VC. These findings provide an insight into the association between PTH and cardiovascular disease.