Linked Life Data

14656654

Source:http://linkedlifedata.com/resource/pubmed/id/14656654

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-5
pubmed:abstractText
In this study we investigated the effect of NF-kB signaling blockade on polymethylmethacrylate (PMMA) particle-induced osteoclastogenesis in vitro. We first established effective blockade of NF-kB activity as tested by electrophoretic mobility shift assays (EMSA). Particle-induced NF-kB activation in murine osteoclast precursor cells (CSF-1-dependent bone marrow macrophages) was markedly reduced by co-treatment of the cells with the NF-kB inhibitors N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and Calpain Inhibitor I (CPI). This inhibition of NF-kB activity was associated with blockade of p50 NF-kB subunit nuclear translocation. We then established a direct NF-kB inhibition approach by utilizing a TAT-bound, mutant IkB (TAT:IkB(46-317)), and demonstrated an inhibitory effect evidenced by decreased NF-kB DNA binding activity. Having established that these strategies (TPCK, CPI, TAT: IkB(46-317)) effectively block NF-kB activation, we next investigated the effect of these agents on particle-stimulated osteoclast formation. PMMA particle stimulation of mature osteoclast formation from RANKL-primed osteoclast precursor cells was blocked by all three inhibitors. To further test the efficacy of NF-kB blockade, experiments were performed with the TAT:IkB(46-317) mutant peptide in whole bone marrow cultures that contain supporting stromal cells. Again, this inhibitor efficiently blocked particle-induced osteoclastogenesis. Thus, we have shown that pharmaceutical and molecular blockade of NF-kB activation inhibits PMMA particle-directed osteoclastogenesis in vitro.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0736-0266
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13-20
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
NF-kB signaling blockade abolishes implant particle-induced osteoclastogenesis.
pubmed:affiliation
Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University School of Medicine, One Barnes-Jewish Hospital Plaza, Suite 11300, West Pavillion, St. Louis, MO 63110, USA. jclohisy@msnotes.wustl.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't