Biggs Manus J P, Richards R Geoff, Gadegaard Nikolaj, Wilkinson Chris D W, Oreffo Richard O C, Dalby Matthew J
Centre for Cell Engineering, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, UK.
Biomaterials. 2009 Oct;30(28):5094-103. doi: 10.1016/j.biomaterials.2009.05.049. Epub 2009 Jun 21.
The physiochemical characteristics of a material with in vivo applications are critical for the clinical success of the implant and regulate both cellular adhesion and differentiated cellular function. Topographical modification of an orthopaedic implant may be a viable method to guide tissue integration and has been shown in vitro to dramatically influence osteogenesis, inhibit bone resorption and regulate integrin mediated cell adhesion. Integrins function as force dependant mechanotransducers, acting via the actin cytoskeleton to translate tension applied at the tissue level to changes in cellular function via intricate signalling pathways. In particular the ERK/MAPK signalling cascade is a known regulator of osteospecific differentiation and function. Here we investigate the effects of nanoscale pits and grooves on focal adhesion formation in human osteoblasts (HOBs) and the ERK/MAPK signalling pathway in mesenchymal populations. Nanopit arrays disrupted adhesion formation and cellular spreading in HOBs and impaired osteospecific differentiation in skeletal stem cells. HOBs cultured on 10 microm wide groove/ridge arrays formed significantly less focal adhesions than cells cultured on planar substrates and displayed negligible differentiation along the osteospecific lineage, undergoing up-regulations in the expression of adipospecific genes. Conversely, osteospecific function was correlated to increased integrin mediated adhesion formation and cellular spreading as noted in HOBS cultured on 100 microm wide groove arrays. Here osteospecific differentiation and function was linked to focal adhesion growth and FAK mediated activation of the ERK/MAPK signalling pathway in mesenchymal populations.
具有体内应用的材料的物理化学特性对于植入物的临床成功至关重要，并调节细胞粘附和分化细胞功能。骨科植入物的表面形貌修饰可能是引导组织整合的一种可行方法，并且已在体外显示出可显著影响骨生成、抑制骨吸收并调节整合素介导的细胞粘附。整合素作为力依赖性机械转导器，通过肌动蛋白细胞骨架起作用，将在组织水平施加的张力通过复杂的信号通路转化为细胞功能的变化。特别是ERK/MAPK信号级联是骨特异性分化和功能的已知调节因子。在这里，我们研究了纳米级凹坑和沟槽对人成骨细胞（HOB）中粘着斑形成以及间充质群体中ERK/MAPK信号通路的影响。纳米凹坑阵列破坏了HOB中的粘着斑形成和细胞铺展，并损害了骨骼干细胞中的骨特异性分化。在10微米宽的沟槽/脊阵列上培养的HOB形成的粘着斑明显少于在平面基质上培养的细胞，并且沿骨特异性谱系的分化可忽略不计，脂肪特异性基因的表达上调。相反，如在100微米宽的沟槽阵列上培养的HOB中所观察到的，骨特异性功能与整合素介导的粘着斑形成增加和细胞铺展相关。在这里，骨特异性分化和功能与粘着斑生长以及间充质群体中ERK/MAPK信号通路的FAK介导的激活有关。
