Apoptosis and survival of osteoblast-like cells are regulated by surface attachment
Apoptosis and survival of osteoblast-like cells are regulated by surface attachment
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DOI：
10.1074/jbc.m402550200
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发表时间：
2005-01-21
影响因子：
4.8
通讯作者：
Adams, CS
中科院分区：
文献类型：
--
作者：
Grigoriou, V;Shapiro, IM;Adams, CS
我们验证了RGDS肽在培养中调节成骨细胞存活的假设。成骨细胞样MC3T3-E1细胞被允许附着在RGDS肽上，RGDS肽通过先前描述的嫁接技术连接到硅胶表面。rgds修饰的表面引起α (v) β(3)整合素的上调。我们注意到活化的局灶黏附激酶和活化的Akt的表达增加。抗凋亡蛋白Bcl-2、促凋亡蛋白Bad及Bad的灭活形式pBad的表达水平均无变化。rgds处理后的膜完全消除了由staurosporine、Ca2+ P-i离子对和硝普钠诱导的细胞凋亡。然而，表面修饰不干扰游离RGDS肽或无血清培养基介导的细胞凋亡。当磷脂酰肌醇3激酶通路活性被抑制时，RGDS依赖性的细胞凋亡抗性被消除。这些结果表明，RGDS通过线粒体途径抑制细胞凋亡，细胞凋亡的抑制依赖于磷脂酰肌醇3-激酶的活性。
We tested the hypothesis that RGDS peptides regulate osteoblast survival in culture. Osteoblast-like MC3T3-E1 cells were allowed to attach to RGDS peptides that had been tethered to a silicone surface utilizing a previously described grafting technique. The RGDS-modified surface caused up-regulation of alpha(v)beta(3) integrin. We noted that there was an increase in expression of activated focal adhesion kinase and activated Akt. There was no change in the expression level of the anti-apoptotic protein Bcl-2, the pro-apoptotic protein Bad, or the inactivated form of Bad, pBad. Attachment to the RGDS-treated membrane completely abolished apoptosis induced by staurosporine, the Ca2+ P-i ion pair, and sodium nitroprusside. However, the surface modification did not interfere with apoptosis mediated by the free RGDS peptide or serum-free medium. When the activity of the phosphatidylinositol 3-kinase pathway was inhibited, RGDS- dependent resistance to apoptosis was eliminated. These results indicated that the binding of cells to RGDS abrogated apoptosis via the mitochondrial pathway and that the suppression of apoptosis was dependent on the activity of phosphatidylinositol 3-kinase.