Effects of polyethylene and TiAlV wear particles on expression of RANK, RANKL and OPG mRNA.
BACKGROUND
Wear debris has been associated with periprosthetic osteolysis and loosening of total joint arthroplasties. RANKL (receptor activator of NF-kappaB ligand), RANK (receptor activator of NF-kappaB) and OPG (osteoprotegerin) are three key molecules which regulate differentiation, survival, fusion, and activation of osteoclasts.


METHODS
We evaluated the effect of TiAIV 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 TiAIV particles. The supernantant was used for measurement of TNFalpha 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 TiAIV particles induced a significant release of TNFalpha after 6 h of exposure and a significant upregulation of RANK mRNA. OPG mRNA expression was transiently upregulated after exposure to polyethylene and TiAIV 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.


CONCLUSIONS
Our findings provide evidence that both polyethylene and TiAIV particles induce upregulation of RANK expression in cells of the monocytic lineage, which may be important for periprosthetic osteoclastogenesis.
Baumann
Bernd
B
Department of Orthopedic Surgery, König-Ludwig-Haus, Julius Maximilians University, Würzburg, Germany. b-baumann.klh@mail.uni-wuerzburg.de
Rader
Christof P
CP
Seufert
Jochen
J
Nöth
Ulrich
U
Rolf
Olaf
O
Eulert
Jochen
J
Jakob
Franz
F
D000497:Alloys; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D005547:Foreign Bodies; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics*; D010010:Osteoclasts / Q000187:drug effects*; D053244:Osteoprotegerin; D020959:Polyethylene / Q000494:pharmacology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects*; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018124:Receptors, Tumor Necrosis Factor; D014025:Titanium / Q000494:pharmacology*
D000497:Alloys; D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D020959:Polyethylene; D014025:Titanium