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Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.

机译:骨催化剂在纳米槽表面上培养的骨质促进剂的限制:局灶性粘合成熟的作用。

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摘要

The differentiation of progenitor cells is dependent on more than biochemical signalling. Topographical cues in natural bone extracellular matrix guide cellular differentiation through the formation of focal adhesions, contact guidance, cytoskeletal rearrangement and ultimately gene expression. Osteoarthritis and a number of bone disorders present as growing challenges for our society. Hence, there is a need for next generation implantable devices to substitute for, or guide, bone repair in vivo. Cellular responses to nanometric topographical cues need to be better understood in vitro in order to ensure the effective and efficient integration and performance of these orthopedic devices. In this study, the FDA-approved plastic polycaprolactone was embossed with nanometric grooves and the response of primary and immortalized osteoprogenitor cells observed. Nanometric groove dimensions were 240 nm or 540 nm deep and 12.5 μm wide. Cells cultured on test surfaces followed contact guidance along the length of groove edges, elongated along their major axis and showed nuclear distortion; they formed more focal complexes and lower proportions of mature adhesions relative to planar controls. Down-regulation of the osteoblast marker genes RUNX2 and BMPR2 in primary and immortalized cells was observed on grooved substrates. Down-regulation appeared to directly correlate with focal adhesion maturation, indicating the involvement of ERK 1/2 negative feedback pathways following integrin-mediated FAK activation.
机译:祖细胞的分化依赖于大于生化信号传导。天然骨细胞外基质的地形提示通过形成焦粘连,接触引导,细胞骨骼重排和最终基因表达的形成细胞分化。骨关节炎和许多骨紊乱作为对我们社会日益增加的挑战。因此,需要在体内替代下一代可植入装置或引导骨骼修复。对于纳米型地形提示的细胞反应需要更好地理解体外,以确保这些整形外科器件的有效和有效的整合和性能。在该研究中,FDA批准的塑料聚己内酯用纳米槽压花,并且观察到初级和永生化的骨催化剂细胞的响应。纳米槽尺寸为240nm或540nm深,宽12.5μm。在测试表面上培养的细胞沿着槽边缘的长度沿着槽边缘的触点引导,沿着它们的主轴伸长并显示核变形;它们相对于平面对照形成了更多的焦点和更低的成熟粘连比例。在凹槽的基材上观察到初级和永生化细胞中的成骨细胞标记基因runx2和Bmpr2的下调。下调似乎与局灶性粘附成熟直接相关,表明整联蛋白介导的FAK激活后ERK 1/2负反馈途径的累积。

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