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Tumor necrosis factor‐α mediates polymethylmethacrylate particle‐induced NF‐κB activation in osteoclast precursor cells
Author(s) -
Clohisy John C.,
Teitelbaum Steven,
Chen Shaoping,
Erdmann Jeanne M.,
AbuAmer Yousef
Publication year - 2002
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1016/s0736-0266(01)00088-2
Subject(s) - osteolysis , tumor necrosis factor alpha , osteoclast , transcription factor , nf κb , cytokine , nfkb1 , cancer research , chemistry , microbiology and biotechnology , immunology , signal transduction , biology , medicine , receptor , biochemistry , gene , surgery
Tumor necrosis factor‐α (TNF) is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of implant particle‐induced osteolysis. The nuclear transcription factor NF‐κB mediates TNF signaling and this transcription complex is necessary for osteoclastogenesis. Because polymethylmethacrylate (PMMA) particles cause osteolysis, we reasoned the PMMA would induce NF‐κB 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‐κB. Supershift assays confirm the presence of the p50 and p65 NF‐κB subunits in the activated transcription factor. Particle‐induced NF‐κB 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 (huTNF:Fc) dampens particle‐directed NF‐κB activation and this response is also abrogated in TNF −/− osteoclast precursors. Thus, PMMA particle activation of NF‐κB is a secondary event resulting from enhanced TNF expression and is independent of LPS contamination. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.