RRC ID 19621
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
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 4.522
Times Cited 15
Human and Animal Cells MC3T3-E1 (RCB1126)