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IGF-1和TGFβ1促进“成人”关节软骨修复的潜力:一项体外研究。

The potential of IGF-1 and TGFbeta1 for promoting "adult" articular cartilage repair: an in vitro study.

作者信息

Davies Lindsay C, Blain Emma J, Gilbert Sophie J, Caterson Bruce, Duance Victor C

机构信息

Department of Oral Surgery, Medicine, and Pathology, School of Dentistry, Cardiff University, Heath Park, Cardiff, United Kingdom.

出版信息

Tissue Eng Part A. 2008 Jul;14(7):1251-61. doi: 10.1089/ten.tea.2007.0211.

Abstract

Research into articular cartilage repair, a tissue unable to spontaneously regenerate once injured, has focused on the generation of a biomechanically functional repair tissue with the characteristics of hyaline cartilage. This study was undertaken to provide insight into how to improve ex vivo chondrocyte amplification, without cellular dedifferentiation for cell-based methods of cartilage repair. We investigated the effects of insulin-like growth factor 1 (IGF-1) and transforming growth factor beta 1 (TGFbeta1) on cell proliferation and the de novo synthesis of sulfated glycosaminoglycans and collagen in chondrocytes isolated from skeletally mature bovine articular cartilage, whilst maintaining their chondrocytic phenotype. Here we demonstrate that mature differentiated chondrocytes respond to growth factor stimulation to promote de novo synthesis of matrix macromolecules. Additionally, chondrocytes stimulated with IGF-1 or TGFbeta1 induced receptor expression. We conclude that IGF-1 and TGFbeta1 in addition to autoregulatory effects have differential effects on each other when used in combination. This may be mediated by regulation of receptor expression or endogenous factors; these findings offer further options for improving strategies for repair of cartilage defects.

摘要

关节软骨修复研究一直聚焦于生成具有透明软骨特征的生物力学功能修复组织,关节软骨一旦受损便无法自发再生。本研究旨在深入了解如何在不使细胞去分化的情况下,改进基于细胞的软骨修复方法中离体软骨细胞的扩增。我们研究了胰岛素样生长因子1(IGF-1)和转化生长因子β1(TGFβ1)对从骨骼成熟的牛关节软骨分离出的软骨细胞增殖以及硫酸化糖胺聚糖和胶原蛋白从头合成的影响,同时维持其软骨细胞表型。在此我们证明,成熟分化的软骨细胞对生长因子刺激有反应,可促进基质大分子的从头合成。此外,用IGF-1或TGFβ1刺激软骨细胞会诱导受体表达。我们得出结论,IGF-1和TGFβ1除了具有自身调节作用外,联合使用时彼此还有不同的影响。这可能是由受体表达或内源性因子的调节介导的;这些发现为改进软骨缺损修复策略提供了更多选择。

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