Cartilage formation and calcification in arteries of mice lacking matrix Gla protein
Cartilage formation and calcification in arteries of mice lacking matrix Gla protein
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DOI：
10.1080/03008200390181762
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发表时间：
2003-01-01
影响因子：
2.9
通讯作者：
McKee, MD
中科院分区：
文献类型：
--
作者：
El-Maadawy, S;Kaartinen, MT;McKee, MD
基质Gla蛋白（MGP/Mgp）是主要由血管平滑肌细胞（VSMC）和软骨细胞表达的蛋白质。缺乏Mgp的转基因小鼠在出生后1-3个月死亡，原因是弹性纤维钙化和大弹性动脉如主动脉破裂[6]。在这里，我们报告软骨形成，通常发生在钙化动脉的Mgp-/-小鼠。使用组织学，von Kossa染色，免疫组织化学，和Western印迹，连同检查VSMC的细胞标志物和软骨的细胞外基质标志物，我们提供的证据，从VSMC的细胞转化为软骨细胞在动脉介质中的Mgp的情况下。在2周龄时，在Mgp-/-小鼠的主动脉中，VSMC失去平滑肌α-肌动蛋白的免疫染色，同时出现软骨分子，如通过聚集蛋白聚糖、连接蛋白和II型胶原的免疫组织化学染色和蛋白质印迹所示。这些数据提供的证据表明，在动脉介质中不存在Mgp和/或ECM钙化可以触发血管中的软骨细胞分化和软骨形成。
Matrix Gla protein (MGP/Mgp) is a protein expressed predominantly by vascular smooth muscle cells (VSMCs) and by chondrocytes. Transgenic mice lacking Mgp die 1-3 months after birth due to calcification of elastic fibers and rupture of large elastic arteries such as the aorta [6]. Here, we report on cartilage formation that commonly occurs in calcified arteries of Mgp-/- mice. Using histology, von Kossa staining, immunohistochemistry, and Western blotting, together with examination of cellular markers for VSMCs and extracellular matrix markers for cartilage, we provide evidence for cell transformation from VSMC to chondrocyte in the arterial media in the absence of Mgp. At 2 weeks of age in the aorta of Mgp-/- mice, VSMCs lose immunostaining for smooth muscle alpha-actin concomitant with the appearance of cartilage molecules as shown by immunohistochemical staining and Western blotting for aggrecan, link protein, and type II collagen. These data provide evidence that the absence of Mgp, and/or calcification of the ECM, in the arterial media can trigger chondrocyte differentiation and cartilage formation in blood vessels.