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.

The Role of Aluminium Ceramics in Total Hip Arthroplasty

“…Hatton et al (2003) on the other hand identified particles from ceramics in two magnitudes by a laser-based micro-dissection method (likewise on failing Mittelmeierprostheses), one group with a mean diameter of 0.503 µm, while the other group showed a diameter on the nanometre scale (24 ± 19 nm). The signalling pathways that have been investigated until now in cell-particle co-culture systems mainly contain cytokines (interleukins, TNF-α), prostaglandins and recently the RANK(L)/OPG-system, too, which so far, however, has only been tested on metallic and polyethylene particles (Baumann et al 2004) and not as yet on aluminium ceramics. On this occasion, an increased expression resp.…”

“…More often particle studies have been carried out with THP-1 cells using other substances than PMA for the stimulation to macrophage-like cells. A research group from Würzburg, Germany, used THP-1 cells which had been pre-treated by a granulocyte macrophage colony-stimulating-factor (GM-CSF) and vitamin D 3 (Baumann et al 2004). …”

Inhibiting wear particles-induced osteolysis with naringin

“…In detail, wear debris stimulates macrophage and other inflammatory cells to produce inflammatory cytokines, such as interleukin (IL)-1, IL-6, and TNF-α [4]. These inflammatory cytokines stimulate osteoblasts and stromal cells to produce large amounts of receptor activator of NF-КB ligand (RANKL) [5][6][7], a key player in initiating enhanced osteoclastogenesis and osteolysis.…”

Recovery of low volumes of wear debris from rat stifle joint tissues using a novel particle isolation method

“…However, the extent of adverse reactions to wear debris is likely to be underestimated, as this was not an option on the revision report forms in the early phase of the National Joint Registry. Several reasons for revision are often given and categories are not mutually exclusive; aseptic loosening and other cited reasons including pain (22.0% of single-stage THR revisions) and lysis (15.6%) are often the result of reactions to wear debris [2,3]. Device failure may be due to a combination of mechanical failure, resulting in high wear, and adverse responses to the wear particles, due to use of potentially unsafe materials.…”