Titanium particles modulate expression of Toll-like receptor proteins
Jukka Pajarinen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
Search for more papers by this authorZygmunt Mackiewicz
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
Vilnius University Institute of Experimental and Clinical Medicine, Vilnius, Lithuania
Search for more papers by this authorRaimo Pöllänen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
Search for more papers by this authorMichiaki Takagi
Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
Search for more papers by this authorNoah J. Epstein
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorTing Ma
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorStuart B. Goodman
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorCorresponding Author
Yrjö T. Konttinen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
COXA Hospital for Joint Replacement, Tampere, Finland
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, FinlandSearch for more papers by this authorJukka Pajarinen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
Search for more papers by this authorZygmunt Mackiewicz
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
Vilnius University Institute of Experimental and Clinical Medicine, Vilnius, Lithuania
Search for more papers by this authorRaimo Pöllänen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
Search for more papers by this authorMichiaki Takagi
Department of Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan
Search for more papers by this authorNoah J. Epstein
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorTing Ma
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorStuart B. Goodman
Department of Orthopaedic Surgery, Stanford University, Stanford, California
Search for more papers by this authorCorresponding Author
Yrjö T. Konttinen
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, Finland
ORTON Orthopaedic Hospital of the Orton Foundation, Helsinki, Finland
COXA Hospital for Joint Replacement, Tampere, Finland
Department of Medicine (Rheumatology), Institute of Clinical Medicine, Biomedicum Helsinki, University of Helsinki, FinlandSearch for more papers by this authorAbstract
The role of Toll-like receptors (TLRs) responding to microbial remnants, indolent biofilms or cellular byproducts in aseptic loosening of joint replacements is unknown. Thus, the effect of titanium (Ti) particles on TLR protein levels was evaluated. To create a model of particle-induced inflammation, an intramedullary stainless steel rod with and without Ti particles was bilaterally placed in the femora of 14 mice. The animals were sacrificed at 2 or 10 weeks postoperatively and paraffin-embedded femur sections were evaluated for TLR1, 2, 4, 5, 8, and 9 proteins using immunohistochemistry. Decrease in the number of TLR immunoreactive cells was observed between weeks 2 and 10 in both settings. Furthermore, in the presence of Ti particles, the numbers of TLR immunoreactive cells were lower than in the presence of rod only at both time points, suggesting downregulation of TLR expression by Ti-particles per se. Accordingly, in a short-term 24 h stimulation, downregulation of TLR4 mRNA (p < 0.02) was observed in vitro in RAW 264.7 cells challenged with Ti particles. Results suggest that after an initial inflammatory stage, TLRs are downregulated in response to Ti particles, possibly to inhibit excessive inflammation, although TLR downregulation might at the same time render tissues more susceptible to pathogens. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
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