Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.
Osteogenic lineage restriction by osteoprogenitors cultured on nanometric grooved surfaces: the role of focal adhesion maturation.
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DOI：
10.1016/j.actbio.2013.11.008
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发表时间：
2014-02
影响因子：
9.7
通讯作者：
Dalby, Matthew J.
中科院分区：
文献类型：
--
作者：
Cassidy, John W.;Roberts, Jemma N.;Smith, Carol-Anne;Robertson, Mary;White, Kate;Biggs, Manus J.;Oreffo, Richard O. C.;Dalby, Matthew J.
祖细胞的分化不仅仅依赖于生物化学信号。天然骨细胞外基质中的地形线索通过形成粘着斑、接触引导、细胞骨架重排和最终基因表达来引导细胞分化。骨关节炎和一些骨疾病目前作为日益增长的挑战，我们的社会。因此，需要下一代可植入装置来替代或引导体内骨修复。为了确保这些骨科器械的有效和高效整合和性能，需要在体外更好地了解细胞对纳米形貌线索的反应。在这项研究中，FDA批准的塑料聚己内酯浮雕纳米凹槽和原代和永生化骨祖细胞的反应进行了观察。纳米沟槽尺寸为240 nm或540 nm深和12.5 μm宽。在测试表面上培养的细胞遵循沿着凹槽边缘长度的接触引导，沿着其主轴伸长并显示核变形;相对于平面对照，它们形成更多的局灶性复合体和较低比例的成熟粘连。在有凹槽的基质上观察到成骨细胞标记基因RUNX 2和BMPR 2在原代和永生化细胞中的下调。下调似乎与粘着斑成熟直接相关，表明整合素介导的FAK激活后ERK 1/2负反馈通路的参与。
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.
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影响因子：
3.4
作者：
Besser, A;Safran, SA
通讯作者：
Safran, SA
影响因子：
--
作者：
Hootman, JM;Helmick, CG
通讯作者：
Helmick, CG
DOI：
10.1083/jcb.200610046
发表时间：
2007-02-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
通讯作者：
Franceschi RT
影响因子：
11.2
作者：
Jiang Ming-Wei;Guo Cheng-Gong;Wang Cai-Qi
通讯作者：
Wang Cai-Qi
影响因子：
5.4
作者：
Biggs, Manus Jonathan Paul;Richards, R. Geoff;Dalby, Matthew J.
通讯作者：
Dalby, Matthew J.