TGF-b-activated kinase 1 mediates mechanical stress-induced XXXX expression in osteoblasts.

@entity19 @entity10180 @entity22617 @entity10756 @entity14374 @entity777 @entity141 @entity1995
Mechanical stress plays a key role in bone remodeling. Previous studies showed that loading of mechanical stretch induces a rapid @entity141 influx and subsequent activation of stress-activated protein kinase pathways in osteoblasts. However, the activation mechanism and its significance in bone remodeling have not been fully elucidated. Here we show that @entity10180 MAPKKK was activated by cyclic stretch loading of @entity19 cells. Knockdown of @entity10180 attenuated the stretch-induced activation of JNK, @entity1995 , and NF-kB. Extracellular (EGTA) or intracellular (BAPTA/AM) @entity141 chelator prevented the stretch-induced activation of @entity10180 . Activation of @entity10180 and its associated downstream signaling pathways were also suppressed by @entity22617 inhibitors ( @entity14374 and @entity10756 ). Furthermore, @entity10180 -mediated downstream pathways cooperatively induced the expression of @entity777 mRNA in the stretched @entity19 cells. We also confirmed that @entity10180 mediates cyclic stretch-induced @entity777 protein synthesis in the cells using immunoblotting and ELISA. Finally, stretch loading of @entity19 primary osteoblasts induced the expression of @entity777 mRNA via @entity10180 . Collectively, these data suggest that stretch-dependent @entity141 influx activates @entity10180 via @entity22617 , leading to the enhanced expression of @entity777 through JNK, @entity1995 , and NF-kB pathways in osteoblasts.
