Effects of polyethylene and TiAIV wear particles on expression of RANK, RANKL and OPG mRNA

Abstract

Background Wear debris has been associated with periprosthetic osteolysis and loosening of total joint arthroplasties. RANKL (receptor activator of NF-κB ligand), RANK (receptor activator of NF-κB) and OPG (osteoprotegerin) are three key molecules which regulate differentiation, survival, fusion, and activation of osteoclasts.Material and methods We evaluated the effect of TiAlV and polyethylene particles on expression of RANK, RANKL and OPG mRNA. We used a human monocytic leukemic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated into macrophage-like cells and exposed to polyethylene particles and prosthesis-derived TiAlV particles. The supernantant was used for measurement of TNFα protein and total RNA was extracted from the cells. Expression of the genes coding for OPG, RANKL and RANK was analysed at the mRNA level using a semiquantitative RT-PCR method.Results Both polyethylene and TiAlV particles induced a significant release of TNFα after 6 h of exposure and a significant upregulation of RANK mRNA. OPG mRNA expression was transiently upregulated after exposure to polyethylene and TiAlV particles. These effects were dependent on particle dose. RANKL mRNA was not detectable in our THP-1 model. In contrast, LPS exhibited a different pattern of RANK/RANKL/OPG mRNA expression.Interpretation Our findings provide evidence that both polyethylene and TiAlV particles induce upregulation of RANK expression in cells of the monocytic lineage, which may be important for periprosthetic osteoclastogenesis.