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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
Author(s) -
Lee DingYu,
Yeh ChiuanRen,
Chang ShunFu,
Lee PeiLing,
Chien Shu,
Cheng ChengKung,
Chiu JengJiann
Publication year - 2008
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.080302
Subject(s) - integrin , microbiology and biotechnology , osteopontin , extracellular matrix , chemistry , fibronectin , kinase , mapk/erk pathway , osteoblast , signal transduction , p38 mitogen activated protein kinases , protein kinase a , biology , endocrinology , cell , biochemistry , in vitro
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 α v β 3 and β 1 integrins with Shc, phosphorylation of mitogen‐activated protein kinases (MAPKs, i.e., extracellular signal‐regulated kinase [ERK], c‐ jun ‐NH 2 ‐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 α v β 3 and β 1 with Shc when seeded on FN, but sustained associations of only β 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 Shc, and these pathways differentially modulated the downstream bone formation‐related gene expression. Our findings showed that β 1 integrin plays predominant roles for shear‐induced signaling and gene expression in osteoblast‐like MG63 cells on FN, COL1, and LM and that α v β 3 also plays significant roles for such responses in cells on FN. The β 1 /Shc association leads to the activation of ERK, which is critical for shear induction of bone formation‐related genes in osteoblast‐like cells.