| RRC ID |
18215
|
| Author |
Fukuno N, Matsui H, Kanda Y, Suzuki O, Matsumoto K, Sasaki K, Kobayashi T, Tamura S.
|
| Title |
TGF-β-activated kinase 1 mediates mechanical stress-induced IL-6 expression in osteoblasts.
|
| Journal |
Biochem Biophys Res Commun
|
| Abstract |
Mechanical stress plays a key role in bone remodeling. Previous studies showed that loading of mechanical stretch induces a rapid Ca(2+) 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 TAK1 MAPKKK was activated by cyclic stretch loading of MC3T3-E1 cells. Knockdown of TAK1 attenuated the stretch-induced activation of JNK, p38, and NF-κB. Extracellular (EGTA) or intracellular (BAPTA/AM) Ca(2+) chelator prevented the stretch-induced activation of TAK1. Activation of TAK1 and its associated downstream signaling pathways were also suppressed by CaMKII inhibitors (KN-93 and KN-62). Furthermore, TAK1-mediated downstream pathways cooperatively induced the expression of IL-6 mRNA in the stretched MC3T3-E1 cells. We also confirmed that TAK1 mediates cyclic stretch-induced IL-6 protein synthesis in the cells using immunoblotting and ELISA. Finally, stretch loading of murine primary osteoblasts induced the expression of IL-6 mRNA via TAK1. Collectively, these data suggest that stretch-dependent Ca(2+) influx activates TAK1 via CaMKII, leading to the enhanced expression of IL-6 through JNK, p38, and NF-κB pathways in osteoblasts.
|
| Volume |
408(2)
|
| Pages |
202-7
|
| Published |
2011-5-6
|
| DOI |
10.1016/j.bbrc.2011.02.127
|
| PII |
S0006-291X(11)00346-9
|
| PMID |
21371434
|
| MeSH |
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
Animals
Benzylamines / pharmacology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
Cell Line
Gene Knockdown Techniques
Interleukin-6 / biosynthesis*
MAP Kinase Kinase 4 / metabolism
MAP Kinase Kinase Kinases / genetics
MAP Kinase Kinase Kinases / physiology*
Mice
NF-kappa B / metabolism
Osteoclasts / enzymology
Osteoclasts / physiology*
Stress, Mechanical*
Sulfonamides / pharmacology
p38 Mitogen-Activated Protein Kinases / metabolism
|
| IF |
2.985
|
| Times Cited |
20
|
|
WOS Category
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
MC3T3-E1(RCB1126) |
