A study on response to mechanical stress in human chondrocytes

整合素家族的粘附分子，包括极晚期活化抗原（VLA），已经涉及各种细胞功能。本研究探讨整合素介导的细胞外基质蛋白相互作用对人软骨细胞细胞因子基因表达和剪切力反应的影响。人关节软骨细胞表面表达VLA-1、-2、-3和-5，并能与多种细胞外基质蛋白，尤其是纤维连接蛋白（FN）粘附。此外，GM-CSF和IL.结果表明，在固定化FN上培养软骨细胞可诱导IL-6、ICAM-1和IL-6的表达，而FN的这种诱导作用可被抗整合素α 5链和β 1链的单克隆抗体完全抑制，对关节软骨细胞施加剪切力可导致IL-6、ICAM-1 mRNA的上调，和下调VCAM-这些结果表明，粘附分子在调节炎症细胞因子的产生和对机械应力的反应中起重要作用。软骨细胞

Adhesion molecules of the integrin family, including very late activation antigens (VLA), have been implicated in various cellular functions. In this study, we investigated the contribution of integrin-mediated interaction with ECM proteins to the cytokine gene expression and the response to the shear stress in human chondrocytesHuman articular chondrocytes expressed VLA-1, -2, -3 and -5 on the cell surface, and could adhere to various ECM proteins, especially to fibronectin (FN). Furthermore, the production of GM-CSF and IL.-6 was potently induced by culturing chondrocytes on immobilized FN.This stimulative effect of FN was completely inhibited by an anti-integrin alpha 5 chain mAb, as well as by anti-integrin beta 1 chain mAbs.Application of shear stress to articular chondrocytes resulted in the up regulation of IL-6 ICAM-1 mRNA, and down regulation of VCAM-l.These results indicate an important role of the adhesion molecule in regulating inflammatory cytokine production and response to the mechanical stress by human articular chondrocytes.