Neven E, Dauwe S, De Broe M E, D'Haese P C, Persy V
Department of Pathophysiology, University of Antwerp, Universiteitsplein 1, 2619 Wilrijk, Belgium.
Kidney Int. 2007 Sep;72(5):574-81. doi: 10.1038/sj.ki.5002353. Epub 2007 May 30.
Arterial media calcification is often considered a cell-regulated process resembling intramembranous bone formation, implying a conversion of vascular tissue into a bone-like structure without a cartilage intermediate. In this study, we examined the association of chondrocyte-specific marker expression with media calcification in arterial samples derived from rats with chronic renal failure (CRF) and from human transplant donors. CRF was induced in rats with a diet supplemented with adenine. Vascular calcification was evaluated histomorphometrically on Von Kossa-stained sections and the expression of the chondrocyte markers sox9 and collagen II with the osteogenic marker core-binding factor alpha1 (cbfa1) was determined immunohistochemically. Media calcification was detected in more than half of the rats with CRF. In over half of the rats with severe media calcification, a typical cartilage matrix was found by morphology. All of the animals with severe calcification showed the presence of chondrocyte-like cells expressing the markers sox9, collagen II, and cbfa1. Human aorta specimens showing mild to moderate media calcification also showed sox9, collagen II, and cbfa1 expression. The presence of chondrocytes in association with calcification of the media in aortas of rats with CRF mimics endochondral bone formation. The relevance of this association is further demonstrated by the chondrogenic conversion of medial smooth muscle cells in the human aorta.
动脉中层钙化通常被认为是一个类似于膜内成骨的细胞调节过程，这意味着血管组织可转化为类似骨的结构，而无需软骨中间体。在本研究中，我们检测了软骨细胞特异性标志物表达与慢性肾衰竭（CRF）大鼠及人类移植供体动脉样本中层钙化之间的关联。通过在大鼠饮食中添加腺嘌呤诱导CRF。采用冯·科萨染色切片进行组织形态计量学评估血管钙化情况，并通过免疫组织化学法测定软骨细胞标志物sox9和胶原蛋白II以及成骨标志物核心结合因子α1（cbfa1）的表达。超过半数的CRF大鼠检测到中层钙化。在超过半数有严重中层钙化的大鼠中，通过形态学发现了典型的软骨基质。所有有严重钙化的动物均显示存在表达标志物sox9、胶原蛋白II和cbfa1的软骨样细胞。显示轻度至中度中层钙化的人类主动脉标本也显示出sox9、胶原蛋白II和cbfa1的表达。CRF大鼠主动脉中层钙化与软骨细胞的存在类似于软骨内成骨。人类主动脉中层平滑肌细胞的软骨形成转化进一步证明了这种关联的相关性。
