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The effect of substratum topography on osteoblast adhesion mediated signal transduction and phosphorylation

机译:基质地形对成骨细胞粘附介导的信号转导和磷酸化的影响

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Substratum surface topography is a powerful modulator of cell behaviour, but how it influences intracellular signaling is largely unknown. We investigated the influence of microfabricated topographies on the activation of nonreceptor tyrosine kinases Src, FAK and ERK 1/2, as well as the transcription factor, Runx2, in rat osteoblasts, cultured on substrata that varied in their ability to promote bone-like tissue formation. Total tyrosine phosphorylation increased on grooves, tapered pits, and gap cornered boxes, relative to the levels found on smooth surfaces, with the greatest activity at 1 week. Src levels was higher on smooth than on any other surface, but FAK and ERK 1/2 phosphorylation were highest on groove and gap-cornered boxes up to 6 weeks. Inhibition of Src phosphorylation with PP2 inhibited FAK and ERK 1/2 phosphorylation on grooves, but had no detectable effect on either FAK or ERK 1/2 on smooth substratum. We suggest that osteoblast response to substrata with specific topographical features requires FAK-Y397-Src-Y416 complexes for ERK 1/2 phosphorylation, but on smooth surfaces, Src independent methods of ERK 1/2 activation are present. (c) 2006 Elsevier Ltd. All rights reserved.
机译:基质表面形貌是细胞行为的有力调节剂,但很大程度上如何影响细胞内信号传导尚不清楚。我们研究了微细化的地形对大鼠成骨细胞中非受体酪氨酸激酶Src,FAK和ERK 1/2活化以及转录因子Runx2活化的影响,这些成骨细胞培养在基质上,促进了类骨组织的生长编队。相对于在光滑表面上发现的水平,凹槽,锥形凹坑和间隙拐角盒上的总酪氨酸磷酸化增加,在1周时活性最高。光滑表面上的Src含量高于其他任何表面,但FAK和ERK 1/2磷酸化在凹槽和间隙角盒上最高达到6周。用PP2抑制Src磷酸化可抑制沟上的FAK和ERK 1/2磷酸化,但对光滑基质上的FAK或ERK 1/2均无可检测的作用。我们建议成骨细胞对具有特定地形特征的基质的反应需要FAK-Y397-Src-Y416复合物才能使ERK 1/2磷酸化,但是在光滑表面上,存在Src独立的ERK 1/2活化方法。 (c)2006 Elsevier Ltd.保留所有权利。

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