OSTEOPONTIN PROMOTES VASCULAR CELL-ADHESION AND SPREADING AND IS CHEMOTACTIC FOR SMOOTH-MUSCLE CELLS IN-VITRO
OSTEOPONTIN PROMOTES VASCULAR CELL-ADHESION AND SPREADING AND IS CHEMOTACTIC FOR SMOOTH-MUSCLE CELLS IN-VITRO
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DOI：
10.1161/01.res.74.2.214
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发表时间：
1994-02-01
影响因子：
20.1
通讯作者：
GIACHELLI, CM
中科院分区：
文献类型：
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作者：
LIAW, L;ALMEIDA, M;GIACHELLI, CM
骨桥蛋白是一种含有arg - gly - asp的酸性磷蛋白，最近发现在大鼠动脉新生内膜形成和人类动脉粥样硬化斑块过程中，血管平滑肌中表达上调。功能研究表明，骨桥蛋白对培养的主动脉内皮细胞和主动脉平滑肌细胞的粘附均有促进作用。当含有7 nmol/L和30 nmol/L骨桥蛋白的溶液分别涂覆内皮细胞和平滑肌细胞孔时，血管细胞对骨桥蛋白的粘附是剂量依赖性的，并且达到了一半。附着在骨桥蛋白上的平滑肌细胞在60分钟后扩散，而内皮细胞在这个时间点虽然变平，但仍保持圆形，但在90分钟时扩散。细胞在骨桥蛋白上扩散并伴有局灶性黏附斑块的形成。一种新开发的抗骨桥蛋白抗体完全抑制两种细胞对骨桥蛋白的粘附，但对纤维连接蛋白或玻璃体连接蛋白不起作用。此外，肽GRGDSP阻断骨桥蛋白粘附，提示整合素介导arg - gly - asp依赖性粘附。事实上，一种针对α， β，整合素的抗体使内皮细胞和平滑肌细胞对骨桥蛋白的粘附减少了约50%，这表明（α, β(3)）是血管细胞上的一种骨桥蛋白受体。骨桥蛋白也促进了平滑肌细胞在boyden型腔室中的迁移，在77 nmol/L的骨桥蛋白中观察到一半的效果。棋盘分析表明，这种刺激在本质上是趋化的。我们的研究结果表明，骨桥蛋白作为血管细胞的粘附和趋化分子可能具有重要的功能，特别是当骨桥蛋白水平急剧增加时，如动脉血管成形术和动脉粥样硬化斑块的情况。
Osteopontin is an Arg-Gly-Asp-containing acidic phosphoprotein recently shown to be upregulated in vascular smooth muscle during rat arterial neointima formation and in human atherosclerotic plaques. Functional studies showed that osteopontin promoted adhesion of both cultured aortic endothelial cells and aortic smooth muscle cells. Adhesion of vascular cells to osteopontin was dose dependent and half maximal when solutions containing 7 and 30 nmol/L osteopontin were used to coat wells for endothelial and smooth muscle cells, respectively. Smooth muscle cells adherent to osteopontin were spread after 60 minutes, whereas endothelial cells remained round, although flattened, at this time point but were spread at 90 minutes. Cell spreading on osteopontin was accompanied by the formation of focal adhesion plaques. A newly developed anti-osteopontin antibody completely inhibited adhesion of both cell types to osteopontin but not to fibronectin or vitronectin. In addition, the peptide GRGDSP blocked adhesion to osteopontin, suggesting that integrins mediate Arg-Gly-Asp-dependent adhesion. Indeed, an antibody against the alpha,beta, integrin neutralized adhesion of both endothelium and smooth muscle cells to osteopontin by approximate to 50%, demonstrating that (alpha,beta(3) is one osteopontin receptor on vascular cells. Osteopontin also promoted the migration of smooth muscle cells in a Boyden-type chamber, with half-maximal effects observed at 77 nmol/L osteopontin. Checkerboard analysis demonstrated that this stimulus was chemotactic in nature. Our findings suggest that osteopontin may be functionally important as an adhesive and chemotactic molecule for vascular cells, particularly when levels of osteopontin are dramatically increased, as is the case after arterial angioplasty and in atherosclerotic plaques.