Sens Carla, Huck Katrin, Pettera Stefan, Uebel Stephan, Wabnitz Guido, Moser Markus, Nakchbandi Inaam A
From the Max-Planck Institute of Biochemistry, 82152 Martinsried and.
the Institute of Immunology, University of Heidelberg, 69120 Heidelberg, Germany.
J Biol Chem. 2017 May 12;292(19):7745-7760. doi: 10.1074/jbc.M116.739987. Epub 2017 Mar 21.
Fibronectin is a multidomain protein secreted by various cell types. It forms a network of fibers within the extracellular matrix and impacts intracellular processes by binding to various molecules, primarily integrin receptors on the cells. Both the presence of several isoforms and the ability of the various domains and isoforms to bind to a variety of integrins result in a wide range of effects. findings suggest that fibronectin isoforms produced by the osteoblasts enhance their differentiation. Here we report that the isoform characterized by the presence of extradomain A activates α4β1 integrin and augments osteoblast differentiation. In addition, the isoform containing extradomain B enhances the binding of fibronectin through the RGD sequence to β3-containing integrin, resulting in increased mineralization by and differentiation of osteoblasts. Our study thus reveals novel functions for two fibronectin isoforms and the mediating receptors in osteoblast differentiation.
纤连蛋白是一种由多种细胞类型分泌的多结构域蛋白。它在细胞外基质中形成纤维网络，并通过与各种分子（主要是细胞上的整合素受体）结合来影响细胞内过程。几种同工型的存在以及各种结构域和同工型与多种整合素结合的能力导致了广泛的效应。研究结果表明，成骨细胞产生的纤连蛋白同工型可增强其分化。在此我们报告，以额外结构域A的存在为特征的同工型可激活α4β1整合素并增强成骨细胞分化。此外，含有额外结构域B的同工型通过RGD序列增强纤连蛋白与含β3整合素的结合，导致成骨细胞矿化增加和成骨细胞分化。因此，我们的研究揭示了两种纤连蛋白同工型和介导受体在成骨细胞分化中的新功能。
