Osteopontin regulates macrophage activation and osteoclast formation in hypertensive patients with vascular calcification.
Osteopontin regulates macrophage activation and osteoclast formation in hypertensive patients with vascular calcification.
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骨桥蛋白调节高血压血管钙化患者的巨噬细胞活化和破骨细胞形成
DOI：
10.1038/srep40253
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发表时间：
2017-01-16
影响因子：
4.6
通讯作者：
Gao PJ
中科院分区：
文献类型：
--
作者：
Ge Q;Ruan CC;Ma Y;Tang XF;Wu QH;Wang JG;Zhu DL;Gao PJ
血管钙化(Vc)是一种高度调控的异位矿物质沉积过程，涉及免疫细胞在血管中的渗透，已被认为是高血压的促进因素。基质细胞糖蛋白骨桥蛋白(OPN)在髓系细胞中被强烈诱导，作为一种潜在的血管损伤炎症介质。本研究旨在探讨OPN是否参与调节高血压合并VC患者的巨噬细胞活化和破骨细胞形成。我们首先通过流式细胞术分析发现伴有VC的高血压患者外周血中CD11c+CD163-促炎性单核细胞的比例高于无VC的患者。高血压合并VC患者的原代培养巨噬细胞也表现出炎症因子表达谱的改变和血清OPN水平的升高。外源性OPN促进外周血单核细胞分化为另一种抗炎表型，并抑制这些VC患者的巨噬细胞向破骨细胞的分化。此外，在高血压患者中，钙化血管表现为破骨细胞聚集增加，巨噬细胞浸润减少。综上所述，OPN在高血压合并VC患者的单核/巨噬细胞表型分化中发挥重要作用，包括减少炎症因子的表达和减少破骨细胞的形成。
Vascular calcification (VC) is a highly regulated ectopic mineral deposition process involving immune cell infiltration in the vasculatures, which has been recognized to be promoted by hypertension. The matricellular glycoprotein osteopontin (OPN) is strongly induced in myeloid cells as a potential inflammatory mediator of vascular injury. This study aims to examine whether OPN is involved in the regulation of macrophage activation and osteoclast formation in hypertensive subjects with VC. We firstly found an increased proportion of CD11c+CD163- pro-inflammatory peripheral monocytes in hypertensive subjects with VC compared to those without VC by flow cytometric analysis. Primary cultured macrophages from hypertensive subjects with VC also showed altered expression profile of inflammatory factors and higher serum OPN level. Exogenous OPN promoted the differentiation of peripheral monocytes into an alternative, anti-inflammatory phenotype, and inhibited macrophage-to-osteoclast differentiation from these VC patients. In addition, calcified vessels showed increased osteoclasts accumulation accompanied with decreased macrophages infiltration in the of hypertensive subjects. Taken together, these demonstrated that OPN exerts an important role in the monocytes/macrophage phenotypic differentiation from hypertensive patients with VC, which includes reducing inflammatory factor expression and attenuating osteoclast formation.