Tumor necrosis factor (TNF) plays a fundamental role in the pathogenesis of wear particle-induced periprosthetic osteolysis. However, particle-induced mechanisms that control TNF gene expression are not yet well characterized. LITAF [lipopolysaccharide (LPS)-induced TNF factor] is a novel transcription factor that regulates expression of the TNF gene, but nothing is known about its role in wear particle-induced osteolysis. We evaluated the effect of titanium aluminum vanadium (TiAlV) and polyethylene particles on mRNA expression of LITAF. A human monocytic leukemia cell line (THP-1) was used in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to LPS-detoxified polyethylene particles and prosthesis-derived TiAlV particles. Supernatant was used for TNF protein measurement and total RNA was extracted from cells. LITAF was analyzed at the mRNA level using semiquantitative RT-PCR. Both polyethylene and TiAlV particles induced significant upregulation of LITAF mRNA that was followed by a significant TNF response. These effects were dependent on the particle dose. Low particle concentrations exhibited no significant effect on expression of TNF and LITAF mRNA. In comparison to exposure to polyethylene and TiAlV particles, LPS stimulation exhibited similar upregulation of LITAF mRNA, but led to an overwhelming TNF response. Our findings provide evidence that LITAF is implicated in the pathogenesis of wear particle-induced osteolysis.
Print ISSN: 0013-5585
Volume: 52, 04/2007
Pages: 200 - 207