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Ann N Y Acad Sci. 2007 Nov;1117:143-50.

Orthopedic implant particle-induced tumor necrosis factor-alpha production in macrophage-monocyte lineage cells is mediated by nuclear factor of activated T cells.

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Center for Orthopedic Research, Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA.

Erratum in

  • Ann N Y Acad Sci. 2011 Jun;1228:179. Young-In Lee, Francis [corrected to Lee, Francis Young].


Wear particles produced from artificial joint prostheses are known to cause macrophage-monocyte lineage cells to produce proosteoclastogenic cytokines, including tumor necrosis factor (TNF)-alpha. The specific molecular mechanism, however, is not yet known. Bioinformatic analysis showed that the promoter region of TNF-alpha has several consensus sequences for NFAT binding. Consequently, we examined the role of nuclear factor of activated T cells (NFAT) in TNF-alpha production. Our investigation has shown that treatment with titanium nanoparticles increased TNF-alpha gene expression along with TNF-alpha protein secretion in murine macrophage-like RAW264.7 and primary monocyte-macrophage cells. Titanium particle-induced TNF-alpha induction was inhibited by VIVIT, a peptide inhibitor that targets the calcineurin/NFAT axis, which suggests that NFAT mediates metallic particle-induced TNF-alpha expression in monocyte-macrophage lineage cells.

[Indexed for MEDLINE]

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