Reference - Detail
RRC ID | 19621 |
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Author | Hou CH, Lin J, Huang SC, Hou SM, Tang CH. |
Title | Ultrasound stimulates NF-kappaB activation and iNOS expression via the Ras/Raf/MEK/ERK signaling pathway in cultured preosteoblasts. |
Journal | J Cell Physiol |
Abstract |
It has been shown that ultrasound (US) stimulation accelerates fracture healing in the animal models and non-operatively clinical uses. Nitric oxide (NO) is a crucial early mediator in mechanically induced bone formation. Here we found that US-mediated inducible nitric oxide synthase (iNOS) expression was attenuated by Ras inhibitor (manumycin A), Raf-1 inhibitor (GW5074), MEK inhibitor (PD98059), NF-kappaB inhibitor (PDTC), and IkappaB protease inhibitor (TPCK). US-induced Ras activation was inhibited by manumycin A. Raf-1 phosphorylation at Ser(338) by US was inhibited by manumycin A and GW5074. US-induced MEK and ERK activation was inhibited by manumycin A, GW5074, and PD98059. Stimulation of preosteoblasts with US activated IkappaB kinase alpha/beta (IKK alpha/beta), IkappaBalpha phosphorylation, p65 phosphorylation at Ser(276), p65, and p50 translocation from the cytosol to the nucleus, and kappaB-luciferase activity. US-mediated an increase of IKK alpha/beta, IkappaBalpha, and p65 phosphorylation, kappaB-luciferase activity and p65 and p50 binding to the NF-kappaB element was inhibited by manumycin A, GW5074, and PD98059. Our results suggest that US increased iNOS expression in preosteoblasts via the Ras/Raf-1/MEK/ERK/IKKalphabeta and NF-kappaB signaling pathways. |
Volume | 220(1) |
Pages | 196-203 |
Published | 2009-7-1 |
DOI | 10.1002/jcp.21751 |
PMID | 19288477 |
MeSH | Animals Cell Differentiation* Cell Line Enzyme Induction Extracellular Signal-Regulated MAP Kinases / metabolism* Fracture Healing Genes, Reporter I-kappa B Kinase / metabolism MAP Kinase Signaling System Mice Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors Mitogen-Activated Protein Kinase Kinases / metabolism* NF-kappa B / antagonists & inhibitors NF-kappa B / metabolism* NF-kappa B p50 Subunit / metabolism Nitric Oxide Synthase Type II / biosynthesis* Nitric Oxide Synthase Type II / genetics Osteoblasts / drug effects Osteoblasts / enzymology* Phosphorylation Promoter Regions, Genetic Protein Kinase Inhibitors / pharmacology Transcription Factor RelA / metabolism Transcriptional Activation Transfection Ultrasonics* raf Kinases / antagonists & inhibitors raf Kinases / metabolism* ras Proteins / antagonists & inhibitors ras Proteins / metabolism* |
IF | 5.546 |
Times Cited | 22 |
WOS Category | PHYSIOLOGY CELL BIOLOGY |
Resource | |
Human and Animal Cells | MC3T3-E1(RCB1126) |