Assessment of five interleukins in human synovial fluid as possible markers for aseptic loosening of hip arthroplasty.
ABSTRACT One of the most important factors that seems to be involved in total hip replacement is periprosthetic osteolysis. As it is well documented that several interleukins (ILs) are triggered in periprosthetic osteolysis, this article investigates the role of five ILs in primary and replacement total hip arthroplasty, understanding if one of them can also predict hip implant loosening, secondary surgery, and prosthesis breakage. The levels of IL-1alpha, 1beta, 6, 8, and 10 in synovial fluid were examined, using a high sensitivity enzyme-linked immunosorbent assay (ELISA) test kit (Pierce Biotechnology, Inc., Rockford, IL, USA) to determine whether these cytokines could be used as markers of enhanced periprosthetic osteolysis, leading to aseptic loosening of total/partial hip arthroplasty or revision surgery. Synovial fluid was harvested from 23 patients undergoing primary total hip arthroplasty and 35 patients undergoing total/partial hip revision due to aseptic loosening. In the revision group, four cases had suffered a prosthesis fracture and five were second revisions. ILs 6 and 8 were significantly higher in the revisions (305 and 817 pg/mL) compared with the primary arthroplasties (151 and 151 pg/mL), including cases with prosthesis fracture and those requiring a second revision. IL-10 levels were lower (not significantly) in second revision samples compared with those of revision samples. IL-1beta levels were significantly higher in prosthesis fracture samples compared with those of all the other revision samples. No statistically significant differences in IL levels were found between osteoarthritis samples and those of other diseases. These results are a step forward to elucidating the complex network of events that are involved in loosening of hip implants.
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ABSTRACT: Titanium particles generated from orthopedic and dental implants are suspected to play an important role in peri-implant osteolysis. Elucidation of the mechanisms involved in the effects of titanium particles on osteolysis may provide methods for preventing osteolysis. Therefore, in the present study, we investigated the effect of titanium particles on osteoclast activity in vitro. We evaluated bone resorption pits on dentin slices and osteoclast F-actin rings after treatment with titanium particles. The influence of titanium particles on the expression of TRAP, Cat K and CA II mRNA was also evaluated. We found that osteoclast bone resorption activity was enhanced at a lower concentration of titanium particles, but inhibited by a higher concentration of titanium particles. Titanium particles can be phagocytosed by osteoclasts, but the F-actin ring was not destroyed after phagocytosis. In addition, a lower concentration of titanium particles enhanced the mRNA expression of TRAP and Cat K, while higher concentrations of titanium particles decreased their expression. By contrast, the mRNA expression of CA II was decreased at all concentrations of titanium particles. These results suggest that direct exposure to titanium particles at a low concentration enhances osteoclast activity, while exposure to a high concentration inhibits their activity. This understanding of the direct effect of titanium particles on osteoclast activity suggests that aseptic loosening is caused not only by the generation of osteoclasts, but also by enhanced osteoclast activity.Molecular Medicine Reports 3(6):1065-9. DOI:10.3892/mmr.2010.368 · 1.48 Impact Factor
- Artificial Organs 03/2010; 34(3):242-66. DOI:10.1111/j.1525-1594.2010.01014.x · 1.87 Impact Factor
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ABSTRACT: Aseptic joint loosening is a key factor that reduces the life span of arthroplasty. There are currently few effective treatments for joint loosening except surgical revision. We explored the inhibitory effects of tumor necrosis factor (TNF)-alpha-targeted small interfering RNA (siRNA) on particle-induced inflammatory cytokine expression in the murine macrophage cell line, RAW264.7. siRNA targeting TNF-alpha was chemically synthesized and transfected into RAW264.7 cells by cationic liposomes. Ceramic, titanium, and polyethylene particles of different sizes (0.2-1.2 µm and 1.2-10 µm) were prepared to stimulate cells 24 h after siRNA transfection. The down-regulation of TNF-alpha mRNA and protein levels was quantitatively determined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively, at different time intervals. Fluorescence microscopy showed that the siRNA transfection efficiency was 85.2% ± 3.5%. Real-time PCR showed that the levels of TNF-alpha mRNA in the particle stimulation plus RNA interference (RNAi) groups were significantly lower compared with the particle stimulation-only groups 3 h after stimulation (P < 0.05). Similarly, ELISA essays showed that the protein levels of TNF-alpha in the RNAi-treated groups were significantly decreased 24 h after transfection (P < 0.05). There were no significant differences in the inhibitory effect among the groups stimulated by different particle types or particle sizes (P > 0.05). Our results indicated that siRNA targeting TNF-alpha can inhibit TNF-alpha release from RAW264.7 cells when stimulated by ceramic, titanium, and polyethylene particles of different sizes and that the inhibitory effects were not related to the type or size of particle.Artificial Organs 04/2011; 35(7):706-14. DOI:10.1111/j.1525-1594.2010.01175.x · 1.87 Impact Factor