Integrin-mediated expression of bone formation-related genes in osteoblast-like cells in response to fluid shear stress: Roles of extracellular matrix, Shc, and mitogen-activated protein kinase
Integrin-mediated expression of bone formation-related genes in osteoblast-like cells in response to fluid shear stress: Roles of extracellular matrix, Shc, and mitogen-activated protein kinase
复制标题
DOI：
10.1359/jbmr.080302
复制
发表时间：
2008-07-01
影响因子：
6.2
通讯作者：
Chiu, Jeng-Jiann
中科院分区：
文献类型：
--
作者：
Lee, Ding-Yu;Yeh, Chiuan-Ren;Chiu, Jeng-Jiann
整合素在细胞对细胞外基质（ECM）的机械反应中起重要作用。我们研究了整合素和ECM蛋白（纤连蛋白[FN]、I型胶原[COL 1]和层粘连蛋白[LM]）在人骨肉瘤MG 63细胞中剪切介导的信号传导和骨形成相关基因（早期生长反应-1 [Egr-1]、c-fos、环氧合酶-2 [考克斯-2]和骨桥蛋白[OPN]）表达中的作用。FN、COL 1和LM上的MG 63细胞作为对照或经受剪切应力（12达因/cm（2）），α（v）β（3）和β（1）整合素与She的结合，促分裂原活化蛋白激酶（MAPK，即，细胞外信号调节激酶（ERK）、c-jun-NH 2-末端激酶（JNK）和p38）以及Egr-1、c-fos、考克斯-2和OPN的表达。在MG 63细胞中，当接种在FN上时，剪切应力诱导α（v）β（3）和β（1）与Shc的持续关联，但当接种在COL 1/LM上时，仅β（1）与Shc的持续关联。FN上的细胞中MAPKs和骨形成相关基因的剪切诱导持续（24小时），但其中一些反应在COL 1/LM上的细胞中是短暂的。ERK、JNK和p38的剪切激活是由整合素和She介导的，这些途径差异调节下游骨形成相关基因的表达。我们的研究结果表明，β（1）整联蛋白在FN、COL 1和LM上的成骨细胞样MG 63细胞中对剪切诱导的信号传导和基因表达起主导作用，而α（v）β（3）也在FN上的细胞中的此类反应中发挥重要作用。β（1）/Shc的结合导致ERK的激活，这对于成骨细胞样细胞中骨形成相关基因的剪切诱导至关重要。
Integrins play significant roles in mechanical responses of cells on extracellular matrix (ECM). We studied the roles of integrins and ECM proteins (fibronectin [FN], type I collagen [COL1], and laminin [LM]) in shear-mediated signaling and the expression of bone formation-related genes (early growth response-1 [Egr-1], c-fos, cyclooxygenase-2 [Cox-2], and osteopontin [OPN]) in human osteosarcoma MG63 cells. MG63 cells on FN, COL1, and LM were kept as controls or subjected to shear stress (12 dynes/cm(2)), and the association of alpha(v)beta(3) and beta(1) integrins with She, phosphorylation of mitogen-activated protein kinases (MAPKs, i.e., extracellular signal-regulated kinase [ERK], c-jun-NH2-terminal kinase [JNK], and p38), and expressions of Egr-1, c-fos, Cox-2, and OPN were determined. In MG63 cells, shear stress induces sustained associations of alpha(v)beta(3) and beta(1) with Shc when seeded on FN, but sustained associations of only beta(1) with Shc when seeded on COL1/LM. Shear inductions of MAPKs and bone formation-related genes were sustained (24 h) in cells on FN, but some of these responses were transient in cells on COL1/LM. The shear activations of ERK, JNK, and p38 were mediated by integrins and She, and these pathways differentially modulated the downstream bone formation-related gene expression. Our findings showed that beta(1) integrin plays predominant roles for shear-induced signaling and gene expression in osteoblast-like MG63 cells on FN, COL1, and LM and that alpha(v)beta(3) also plays significant roles for such responses in cells on FN. The beta(1)/Shc association leads to the activation of ERK, which is critical for shear induction of bone formation-related genes in osteoblast-like cells.