title: Focal adhesion kinase signaling pathway is involved in mechanotransduction in MG-63 cells.
abstract: Interstitial fluid flow, generated upon induced movement of extracellular fluid after mechanical loading, activates many signal transduction pathways in bone cells. The mechanisms of mechanobiology in bone tissue are still not clearly understood. Recently focal adhesion kinase (FAK) was shown to be involved in mechanotransduction in a number of cells. This study was designed to characterize the functional roles of FAK in mediating osteoblast response to mechanical steady-state fluid shear stress (FSS). We reported here that FSS (15 dynes/cm(2)) induced activation of FAK and formation of FAK·Grb2·Sos ternary complex in MG-63 cells, which was necessary for activation of the downstream mitogen-activated protein kinase pathway signaling molecules extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). Our results also showed that transfection of FAK (F397Y) plasmid, a negative mutant of FAK, blocked the increased expression of binding factor alpha 1, osterix, osteocalcin and alkaline phosphatase induced by FSS in MG-63 cells. These results demonstrate that FAK signaling is critical for FSS-induced activation of ERK and JNK, and for promotion of osteoblast differentiation and osteogenesis via its association with Grb2/Sos complex.
authors.affiliation: The Key Laboratory of Aerospace Medicine, Chinese Ministry of Education, Xi'an, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Tingyuan
authors.initials: T
authors.lastname: Du
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Wang
authors.forename: Changbin
authors.initials: C
authors.lastname: Yang
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Cao
mesh_terms: D001842:Bone and Bones / Q000201:enzymology / Q000502:physiology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D010006:Osteoblasts / Q000201:enzymology / Q000502:physiology*; D010012:Osteogenesis; D020839:Son of Sevenless Protein, Drosophila / Q000378:metabolism
chemical_list: D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D020839:Son of Sevenless Protein, Drosophila; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4