Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-3-28
pubmed:abstractText
Tumor necrosis factor-alpha (TNF) is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of implant particle-induced osteolysis. The nuclear transcription factor NF-kappaB mediates TNF signaling and this transcription complex is necessary for osteoclastogenesis. Because polymethylmethacrylate (PMMA) particles cause osteolysis, we reasoned the PMMA would induce NF-kappaB activation. In fact, we find that exposure of osteoclast precursors, in the form of colony stimulating factor-1 (CSF-1) dependent murine bone marrow macrophages, to PMMA particles prompts nuclear translocation and activation of NF-kappaB. Supershift assays confirm the presence of the p50 and p65 NF-kappaB subunits in the activated transcription factor. Particle-induced NF-kappaB activation is equal in both wild type and LPS- hyporesponsive cells indicating that the phenomenon does not represent endotoxin contamination. A soluble, competitive inhibitor of TNF (huTNFr:Fc) dampens particle-directed NF-kappaB activation and this response is also abrogated in TNF-/- osteoclast precursors. Thus, PMMA particle activation of NF-kappaB is a secondary event resulting from enhanced TNF expression and is independent of LPS contamination.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0736-0266
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
174-81
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Tumor necrosis factor-alpha mediates polymethylmethacrylate particle-induced NF-kappaB activation in osteoclast precursor cells.
pubmed:affiliation
Department of Orthopaedic Surgery, Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, MO 63110, USA. jclohisy@msnotes.wustl.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't