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首页> 外文期刊>Journal of orthopaedic research >Inhibition of cell-matrix adhesions prevents cartilage chondrocyte death following impact injury
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Inhibition of cell-matrix adhesions prevents cartilage chondrocyte death following impact injury

机译：抑制细胞基质粘附可防止撞击伤后软骨软骨细胞死亡

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Focal adhesions are transmembrane protein complexes that attach chondrocytes to the pericellular cartilage matrix and in turn, are linked to intracellular organelles via cytoskeleton. We previously found that excessive compression of articular cartilage leads to cytoskeleton-dependent chondrocyte death. Here we tested the hypothesis that this process also requires integrin activation and signaling via focal adhesion kinase (FAK) and Src family kinase (SFK). Osteochondral explants were treated with FAK and SFK inhibitors (FAKi, SFKi, respectively) for 2 h and then subjected to a death-inducing impact load. Chondrocyte viability was assessed by confocal microscopy immediately and at 24 h post-impact. With no treatment immediate post-impact viability was 59%. Treatment with 10 μM SFKi, 10 μM, or 100 μM FAKi improved viability to 80%, 77%, and 82%, respectively (p < 0.05). After 24 h viability declined to 34% in controls, 48% with 10 μM SFKi, 45% with 10 μM FAKi, and 56% with 100 μM FAKi (p < 0.01) treatment. These results confirmed that most of the acute chondrocyte mortality was FAK- and SFK-dependent, which implicates integrin-cytoskeleton interactions in the death signaling pathway. Together with previous findings, these data support the hypothesis that the excessive tissue strains accompanying impact loading induce death via a pathway initiated by strain on cell adhesion receptors.
机译：粘着斑是跨膜蛋白复合物，其将软骨细胞附着于细胞周围软骨基质，进而通过细胞骨架与细胞内细胞器相连。我们先前发现关节软骨过度受压会导致细胞骨架依赖性软骨细胞死亡。在这里，我们测试了这一过程还需要整联蛋白激活和通过粘着斑激酶（FAK）和Src家族激酶（SFK）发出信号的假设。骨软骨外植体分别用FAK和SFK抑制剂（分别为FAKi和SFKi）处理2 h，然后施加诱导死亡的冲击负荷。立即和在撞击后24小时通过共聚焦显微镜评估软骨细胞的生存力。如果不进行任何治疗，则立即发生碰撞后的生存力为59％。用10μMSFKi，10μM或100μMFAKi处理可将生存力分别提高至80％，77％和82％（p <0.05）。 24小时后，对照组的存活率下降至34％，使用10μMSFKi处理的存活率降至48％，使用10μMFAKi处理的存活率降至45％，使用100μMFAKi治疗的存活率降至56％（p <0.01）。这些结果证实，大多数急性软骨细胞死亡率是FAK和SFK依赖性的，这暗示了死亡信号通路中整联蛋白-细胞骨架的相互作用。连同先前的发现，这些数据支持这样的假设：伴随冲击负荷的过多组织应变通过细胞粘附受体上的应变引发的途径诱导死亡。

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