TGF-BETA-1 AND 25-HYDROXYCHOLESTEROL STIMULATE OSTEOBLAST-LIKE VASCULAR CELLS TO CALCIFY
TGF-BETA-1 AND 25-HYDROXYCHOLESTEROL STIMULATE OSTEOBLAST-LIKE VASCULAR CELLS TO CALCIFY
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DOI：
10.1172/jci117205
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发表时间：
1994-05-01
影响因子：
15.9
通讯作者：
DEMER, LL
中科院分区：
文献类型：
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作者：
WATSON, KE;BOSTROM, K;DEMER, LL
我们实验室先前的研究证实了人类钙化斑块中骨形态发生蛋白-2a的信使RNA，表明动脉钙化是一个受调节的过程，类似于骨生成。为了进一步验证这一假设，我们从牛主动脉培养基中分离并克隆了一个具有成骨潜能的细胞亚群。这些新细胞主要通过表达表面标记物与平滑肌细胞区分，所述表面标记物初步鉴定为神经节苷脂唾液酸-乳糖神经酰胺（GM 3）的修饰形式。成骨细胞的潜力表明高水平的碱性磷酸酶和胶原蛋白I，骨桥蛋白和骨粘连蛋白（BMP）的表达，骨特异性骨钙素和羟基磷灰石的生产。这些细胞的培养物被氧化固醇25-羟基胆固醇以及转化生长因子β 1刺激形成数量增加的产生钙矿物质的结节，这两种物质都已知存在于动脉粥样硬化病变中。这两种因素对动脉壁钙化血管细胞的刺激提示了体内钙化与动脉粥样硬化共定位的可能机制。
Previous studies in our laboratory demonstrated messenger RNA for bone morphogenetic protein-2a in human calcified plaque, suggesting that arterial calcification is a regulated process, similar to osteogenesis. To further test this hypothesis, we have isolated and cloned a subpopulation of cells from bovine aortic media that show osteoblastic potential. These novel cells are primarily distinguished from smooth muscle cells by expression of a surface marker preliminarily identified as a modified form of the ganglioside sialyl-lactosylceramide (GM3). Osteoblastic potential was indicated by high levels of alkaline phosphatase and collagen I, expression of osteopontin and osteonectin (SPARC), and production of bone-specific osteocalcin and hydroxyapatite. Cultures of these cells were stimulated to form increased numbers of calcium-mineral-producing nodules by the oxysterol 25-hydroxycholesterol as well as by transforming growth factor-beta 1, both known to be present in atherosclerotic lesions. The stimulation of calcifying vascular cells in the artery wall by these two factors suggests a possible mechanism for the colocalization of calcification with atherosclerosis in vivo.