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The transmembrane heparan sulphate proteoglycan syndecan-4 is involved in establishment of the lamellar structure of the annulus fibrosus of the intervertebral disc

机译:跨膜硫酸乙酰肝素蛋白聚糖syndecan-4参与了椎间盘纤维环的层状结构的建立

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The annulus fibrosus of the intervertebral disc unites adjacent vertebral bodies along the length of the spine and provides tensile resistance towards compressive, twisting and bending movements arising through gait. It consists of a nested series of oriented collagenous lamellae, arranged in cross-ply circumferentially around the nucleus pulposus. The organisation of oriented collagen in the annulus is established during foetal development by an identical arrangement of oriented fibroblasts that are precisely organised into cell sheets, or laminae. These provide a template for ordered deposition of extracellular matrix material on cell surfaces, by means of a poorly understood mechanism involving the actin cytoskeleton. In this study, we investigate the role of two cell surface heparan sulphate proteoglycans (HSPGs), glypican-6 and syndecan-4, in the matrix assembly process in the developmental rat intervertebral disc. We compare their expression patterns with those of heparan sulphate and the interactive, cell-surface adhesive glycoprotein, fibronectin, and relate these to the stage-specific collagenous architectures present within the annulus at both light and electron microscopic levels. We show that both proteoglycans are strongly associated with the development, growth and aging of the intervertebral disc. Furthermore, the immunohistochemical labelling patterns suggest that syndecan-4, in particular, plays a potentially-significant role in annulus formation. We propose that this HSPG mediates interaction between the actin cytoskeleton and nascent extracellular matrix in the lamellar organisation of annulus tissue. These data add considerably towards an understanding of how cells organise and maintain complex, oriented extracellular matrices and has particular clinical relevance to the fields of tissue engineering and repair.
机译:椎间盘的纤维环沿着脊柱的长度将相邻的椎体结合在一起,并对步态引起的压缩,扭曲和弯曲运动提供拉伸阻力。它由一系列嵌套的定向胶原薄片组成,围绕髓核周向交叉排列。在胎儿发育过程中,环向胶原蛋白的组织是由定向成纤维细胞的相同排列建立的,该排列被精确地组织成细胞片或薄片。这些通过涉及肌动蛋白细胞骨架的机制缺乏了解,为细胞外基质材料在细胞表面的有序沉积提供了模板。在这项研究中,我们研究了两种细胞表面硫酸乙酰肝素蛋白聚糖(HSPG),glypican-6和syndecan-4在发育中大鼠椎间盘基质组装过程中的作用。我们将它们的表达模式与硫酸乙酰肝素和相互作用的细胞表面粘附性糖蛋白纤连蛋白进行比较,并将它们与光和电子显微镜水平上的环中存在的阶段特异性胶原结构联系起来。我们表明,两种蛋白聚糖都与椎间盘的发育,生长和衰老密切相关。此外,免疫组化标记模式表明,尤其是syndecan-4,在环的形成中起着潜在的重要作用。我们建议这种HSPG介导环组织的层状组织中的肌动蛋白细胞骨架和新生细胞外基质之间的相互作用。这些数据大大增加了对细胞如何组织和维持复杂的定向细胞外基质的了解,并且对组织工程和修复领域具有特殊的临床意义。

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