MAP and src kinases control the induction of AP-1 members in response to changes in mechanical environment in osteoblastic cells

作者：Granet C; Vico AGL; Alexandre C; Lafage Proust MH^*

来源：Cellular Signalling, 2002, 14(8): 679-688.

DOI：10.1016/S0898-6568(02)00008-6

• mechanical deformation
• microgravity
• nuclear translocation
• signal transduction
• mRNA expression
• bone
• c-fos
• c-jun

The activating protein-1 (AP-1) complex plays a critical role in bone physiology, including its response to strain. We Studied gene expression and nuclear translocation kinetics of the seven AP-1 members, after substrate deformation (Flexcell) or stimulated microgravity (Clinostat), in osteoblastic ROS17/2.8 cells. Gene expression and nuclear translocation of all the AP-1 members were induced, under both conditions, with differences in their kinetics, except fosB mRNA in the Clinostat. Downregulation of protein kinase C (PKC) and COX1/2 or inhibition of ERK1/2, p38(MAPK) or src kinases had no major effect oil AP-1 mRNA expression in the Flexcell. In contrast, ERK1/2, p38(MAPK) and si-c kinases treatment blocked nuclear translocation of almost all the AP-1 members in both models, except Fra-1, JunD after deformation and Fra-1, JunB after clinorotation. Thus, changes in the osteoblastic mechanical environment induced a dramatic induction of most of the AP-1 members with specific kinetics and involved MAPK and src kinase pathways, which differed whether the cells were stretched or clinorotated.

• 出版日期2002-8