ADHESIVE AND MIGRATORY EFFECTS OF OSTEOPONTIN ARE MEDIATED VIA DISTINCT CELL-SURFACE INTEGRINS - ROLE OF ALPHA(V)BETA(3) IN SMOOTH-MUSCLE CELL-MIGRATION TO OSTEOPONTIN IN-VITRO
ADHESIVE AND MIGRATORY EFFECTS OF OSTEOPONTIN ARE MEDIATED VIA DISTINCT CELL-SURFACE INTEGRINS - ROLE OF ALPHA(V)BETA(3) IN SMOOTH-MUSCLE CELL-MIGRATION TO OSTEOPONTIN IN-VITRO
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DOI：
10.1172/jci117718
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发表时间：
1995-02-01
影响因子：
15.9
通讯作者：
GIACHELLI, CM
中科院分区：
文献类型：
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作者：
LIAW, L;SKINNER, MP;GIACHELLI, CM
骨桥蛋白是一种含有甘氨酸-天冬氨酸的酸性糖蛋白，被认为在不同组织中介导粘附、迁移和生物矿化。解释这种多功能性的机制还不清楚，尽管已知一种骨桥蛋白受体是α（v）β（3）整联蛋白。在这项工作中，我们研究了α（v）β（3）水平变化的人平滑肌细胞，以鉴定其他骨桥蛋白受体。我们报道，除了α（v）β（3），α（v）β（5）和α（v）β（1）都是骨桥蛋白受体。此外，细胞表面是否存在α（v）β（3）改变了平滑肌细胞对骨桥蛋白的粘附和迁移反应。α（v）β（3）缺陷细胞群对骨桥蛋白的粘附力仅为含有α（v）β（3）的细胞的一半，并且在Boyden室中向骨桥蛋白梯度的迁移依赖于细胞表面α（v）β（3）。尽管α（v）β（3）缺陷的平滑肌细胞不能迁移到骨桥蛋白，但它们确实响应于玻连蛋白和纤连蛋白而显著迁移。这些发现代表了第一次将α（v）β（5）和α（v）β（1）描述为骨桥蛋白受体，并表明，虽然骨桥蛋白的粘附受到含有β（1）、β（3）和β（5）的整合素的支持，但骨桥蛋白的迁移反应似乎依赖于α（v）β（3）。因此，与不同受体的相互作用是骨桥蛋白可以启动多种功能的一种机制。
Osteopontin is an arginine-glycine-aspartate containing acidic glycoprotein postulated to mediate adhesion, migration, and biomineralization in diverse tissues. The mechanisms explaining this multifunctionality are not well understood, although it is known that one osteopontin receptor is the alpha(v) beta(3) integrin, In this work, we studied human smooth muscle cells varying in alpha(v) beta(3) levels to identify additional osteopontin receptors. We report that, in addition to (alpha(v) beta(3), both alpha(v) beta(5) and alpha(v) beta(1) are osteopontin receptors. Moreover, the presence or absence of alpha(v) beta(3) on the cell surface altered the adhesive and migratory responses of smooth muscle cells to osteopontin. Adhesion of alpha(v) beta(3)-deficient cell populations to osteopontin was only half that of cells containing alpha(v) beta(3), and migration toward an osteopontin gradient in the Boyden chamber was dependent on cell surface alpha(v) beta(3). Although alpha(v) beta(3)-deficient smooth muscle cells were unable to migrate to osteopontin, they did migrate significantly in response to vitronectin and fibronectin. These findings represent the first description of alpha(v) beta(5), and alpha(v) beta(1) as osteopontin receptors and suggest that, while adhesion to osteopontin is supported by integrins containing beta(1), beta(3), and beta(5) migration in response to osteopontin appears to depend on alpha(v) beta(3). Thus, interaction with distinct receptors is one mechanism by which osteopontin may initiate multiple functions.