Linked Life Data

11092885

Source:http://linkedlifedata.com/resource/pubmed/id/11092885

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-5-25
pubmed:abstractText
Mechanical loading is crucial for maintenance of bone integrity and architecture, and prostaglandins are an important mediator of mechanosensing. Cyclooxygenase-2 (COX-2), an inducible isoform of prostaglandin G/H synthase, is induced by mechanical loading-derived fluid shear stress in bone-forming cells such as osteoblasts and osteocytes. In this study, we investigated transcription factor and transcriptional regulatory elements responsible for the shear stress-induced COX-2 expression in osteoblastic MC3T3-E1 cells. When the cells were transfected with luciferase-reporter plasmids including the 5'-flanking region of the murine cox-2 gene, the fluid shear stress increased the luciferase activities, consistent with the induction of COX-2 mRNA and protein expression. Deletion analysis of the promoter region revealed that the shear stress-induced luciferase responses were regulated by two regions, -172 to -100 base pair (bp) and -79 to -46 bp, of the cox-2 promoter, in which putative cis-elements of C/EBP beta, AP-1, cAMP-response element-binding protein (CREB), and E box are included. Mutation of sites of C/EBP beta, AP-1, and/or cAMP-response element decreased the shear stress-induced luciferase activities, whereas mutation of the E box did not affect the responses. In an electrophoretic mobility shift assay, shear stress enhanced nuclear extract binding to double-stranded oligonucleotide probes containing C/EBP beta and AP-1-binding motifs, and the bands of the complexes were supershifted by the addition of antibody specific for each regulator. Although the binding activity of CREB toward its probe was unaffected by shear stress, the phosphorylation of CREB was enhanced by the stress. These data suggest that C/EBP beta, AP-1, and CREB play crucial roles in the shear stress-induced cox-2 expression in osteoblasts.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
9
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7048-54
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11092885-Animals, pubmed-meshheading:11092885-Binding Sites, pubmed-meshheading:11092885-Blotting, Western, pubmed-meshheading:11092885-CCAAT-Enhancer-Binding Protein-beta, pubmed-meshheading:11092885-Cell Line, pubmed-meshheading:11092885-Cell Nucleus, pubmed-meshheading:11092885-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:11092885-Cyclooxygenase 2, pubmed-meshheading:11092885-Genetic Vectors, pubmed-meshheading:11092885-Isoenzymes, pubmed-meshheading:11092885-Luciferases, pubmed-meshheading:11092885-Mice, pubmed-meshheading:11092885-Mutation, pubmed-meshheading:11092885-Osteoblasts, pubmed-meshheading:11092885-Plasmids, pubmed-meshheading:11092885-Promoter Regions, Genetic, pubmed-meshheading:11092885-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:11092885-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:11092885-Stress, Mechanical, pubmed-meshheading:11092885-Time Factors, pubmed-meshheading:11092885-Transcription Factor AP-1, pubmed-meshheading:11092885-Transcriptional Activation, pubmed-meshheading:11092885-Transfection, pubmed-meshheading:11092885-Up-Regulation
pubmed:year
2001
pubmed:articleTitle
Fluid shear stress-induced cyclooxygenase-2 expression is mediated by C/EBP beta, cAMP-response element-binding protein, and AP-1 in osteoblastic MC3T3-E1 cells.
pubmed:affiliation
Department of Oral Anatomy, Meikai University School of Dentistry, Sakado, Saitama, Japan.
pubmed:publicationType
Journal Article