A structure-based extracellular matrix expansion mechanism of fibrous tissue growth.
A structure-based extracellular matrix expansion mechanism of fibrous tissue growth.
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DOI：
10.7554/elife.05958
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发表时间：
2015-05-20
期刊：
影响因子：
7.7
通讯作者：
Kadler KE
中科院分区：
文献类型：
--
作者：
Kalson NS;Lu Y;Taylor SH;Starborg T;Holmes DF;Kadler KE
胚胎的生长主要是通过细胞数量的增加来实现的;当纤维组织占成年脊椎动物质量的大部分时，对发育后期的生长机制知之甚少。我们提出了一种基于三维电子显微镜的小鼠肌腱纤维组织生长模型。我们发现，在胚胎发育过程中，胶原纤维的数量增加，然后在出生后的生长过程中保持不变。胚胎生长主要通过原纤维数量和长度的增加来解释。出生后的增长主要来自原纤维长度和直径的增加。螺旋卷曲结构在胚胎发生中建立，并在出生后持续存在。这些数据支持肌腱的形状和大小由胚胎成纤维细胞的数量和位置决定的模型。这些细胞合成的胶原纤维通过基于结构的基质扩张为出生后的生长提供了模板。该模型对其他纤维组织的生长和纤维化具有重要意义。年轻的动物能够以一种允许它们保持大致相同形状的方式生长，直到它们达到成年的大小。胚胎的生长是由细胞大小和数量的增加驱动的，但出生后身体如何生长尚不清楚。此时，体内的许多细胞都是肌腱和其他纤维组织的一部分，它们被胶原蛋白和其他蛋白质组成的纤维网包围。这些纤维为组织提供强度，但也可能限制其生长能力。肌腱连接肌肉和骨骼。它们含有沿着其长度延伸的胶原纤维，这使它们能够应对非常强大的拉力。Kalson等人使用电子显微镜在三个阶段生成高度详细的小鼠肌腱三维模型：胚胎，出生和六周后。实验确定了肌腱发育的两个阶段。在第一阶段，肌腱上的细胞和纤维的数量在胚胎中确定。纤维的直径也会略微扩大，并形成规则的波纹，称为波纹，这对肌腱的结构强度很重要。第二阶段发生在出生后，在此期间，细胞和纤维的数量保持不变，但肌腱继续生长，因为纤维的直径和长度增加。细胞也会移动，形成沿着肌腱的细胞塔。根据这些观察，Kalson等人提出，决定肌腱形状和大小的细胞和胶原纤维的数量和位置是在胚胎中建立的。胶原纤维为出生后肌腱的持续生长创造了一个框架。未来的挑战是了解在胶原纤维形成之前肌腱中细胞的数量和排列是如何确定的，以及这些细胞如何控制形成的胶原纤维的数量。DOI：www.example.com网站
Embryonic growth occurs predominately by an increase in cell number; little is known about growth mechanisms later in development when fibrous tissues account for the bulk of adult vertebrate mass. We present a model for fibrous tissue growth based on 3D-electron microscopy of mouse tendon. We show that the number of collagen fibrils increases during embryonic development and then remains constant during postnatal growth. Embryonic growth was explained predominately by increases in fibril number and length. Postnatal growth arose predominately from increases in fibril length and diameter. A helical crimp structure was established in embryogenesis, and persisted postnatally. The data support a model where the shape and size of tendon is determined by the number and position of embryonic fibroblasts. The collagen fibrils that these cells synthesise provide a template for postnatal growth by structure-based matrix expansion. The model has important implications for growth of other fibrous tissues and fibrosis. DOI: http://dx.doi.org/10.7554/eLife.05958.001 Young animals are able to grow in a way that allows them to maintain roughly the same shape until they reach their adult size. The growth of embryos is driven by increases in cell size and number, but it is less clear how the body grows after birth. By this point, many of the cells in the body are part of tendons and other fibrous tissues, where they are surrounded by a mesh of fibres made of collagen and other proteins. These fibres provide strength to the tissue, but may also restrict its ability to grow. Tendons connect muscles to bones. They contain fibres of collagen that run along their length, which enables them to cope with very strong pulling forces. Kalson et al. used electron microscopy to generate highly detailed three-dimensional models of mouse tendons at three stages: in the embryo, at birth and six weeks later. The experiments identified two stages in tendon development. During the first stage, the number of cells and fibres across the tendon is determined in the embryo. The fibres also slightly expand in diameter and form regular waves called crimps that are important for the structural strength of the tendon. The second stage happens after birth, during which the number of cells and fibres remains constant, but the tendons continue to grow because the fibres increase in diameter and length. The cells also move to form towers of cells running along the tendon. From these observations, Kalson et al. propose that the numbers and locations of the cells and collagen fibres that determine the shape and size of tendons are established in the embryo. The collagen fibres create a framework for the continued growth of the tendon after birth. Future challenges are to understand how the number and the arrangement of cells in the tendon is determined before the collagen fibres are made, and how these cells control the number of collagen fibres that form. DOI: http://dx.doi.org/10.7554/eLife.05958.002