RRC ID 42587
Author Tang CH, Yang RS, Huang TH, Lu DY, Chuang WJ, Huang TF, Fu WM.
Title Ultrasound stimulates cyclooxygenase-2 expression and increases bone formation through integrin, focal adhesion kinase, phosphatidylinositol 3-kinase, and Akt pathway in osteoblasts.
Journal Mol Pharmacol
Abstract It has been shown that ultrasound (US) stimulation accelerates fracture healing in animal models and in clinical studies. Here we found that US stimulation transiently increased the surface expression of alpha2, alpha5, beta1, and beta3 integrins in cultured osteoblasts, as shown by flow cytometric analysis and immunofluorescence staining. US stimulation increased prostaglandin E(2) formation and the protein and mRNA levels of cyclooxygenase-2 (COX-2). At the mechanistic level, anti-integrin alpha5beta1 and alphavbeta3 antibodies or rhodostomin, a snake venom disintegrin, attenuated the US-induced COX-2 expression. Phosphatidylinositol 3-kinase (PI3K) inhibitors 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002) and wortmannin also inhibited the potentiating action of US. US stimulation increased the phosphorylation of focal adhesion kinase (FAK), extracellular signal-regulated kinases (ERK), p85 subunit of PI3K, and serine 473 of Akt. COX-2 promoter activity was enhanced by US stimulation in cells transfected with pCOX2-Luc. Cotransfection with dominant-negative mutant of FAK(Y397F), p85(Deltap85), Akt(K179A), or ERK2(K52R) inhibited the potentiating action of US on COX-2 promoter activity. Expression of mineralized nodule was lower in dominant-negative mutants of FAK, p85, and Akt-transfected clones than in vector-transfected control cells. Taken together, our results provide evidence that US stimulation increases COX-2 expression and promotes bone formation in osteoblasts via the integrin/FAK/PI3K/Akt and ERK signaling pathway.
Volume 69(6)
Pages 2047-57
Published 2006-6
DOI 10.1124/mol.105.022160
PII mol.105.022160
PMID 16540596
MeSH Animals Antibodies, Monoclonal / pharmacology Cell Line Cyclooxygenase 2 / genetics Cyclooxygenase 2 / metabolism* Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / metabolism Focal Adhesion Kinase 1 / antagonists & inhibitors Focal Adhesion Kinase 1 / genetics Focal Adhesion Kinase 1 / metabolism* Integrins / antagonists & inhibitors Integrins / metabolism* Mice NF-kappa B / metabolism Osteoblasts / enzymology Osteoblasts / radiation effects* Osteogenesis / genetics Osteogenesis / radiation effects* Phosphatidylinositol 3-Kinases / metabolism* Phosphoinositide-3 Kinase Inhibitors Promoter Regions, Genetic / radiation effects Proto-Oncogene Proteins c-akt / antagonists & inhibitors Proto-Oncogene Proteins c-akt / metabolism* Rats Signal Transduction Ultrasonics*
IF 3.853
Times Cited 99
Human and Animal Cells