The Expression Levels of Toll-like Receptors after Metallic Particle and Ion Exposition in the Synovium of a Murine Model.

Xiangyun Cheng,Alexander C Paulus,Jan Philippe Kretzer,Rainer Bader,Sandra Utzschneider,Volkmar Jansson

doi:10.3390/jcm10163489

Abstract

To date, the exact role of specific Toll-like receptors (TLRs) in regulating immune reactivity to metallic byproducts of orthopedic implants has not been fully clarified. In light of the situation, our objective in this investigation was to assess the expression levels of surface TLRs after metallic particle and ion exposure in an established animal model. Ten female BALB/c mice in each group received intra-articular injections of phosphate buffer (PBS) (control), metallic particles (MP), and metallic ions (MI), respectively. Seven days later, immunohistochemical staining was undertaken in the synovial layer of the murine knee joints using anti-TLR 1, 2, 4, 5, and 6 polyclonal antibodies. In addition to increased cellular infiltrates and a hyperplastic synovial membrane, the MP group showed significantly elevated TLR expression compared to the control group and had higher TLR 1-, 4-, and 6-positive cells than the MI group (p < 0.0167). TLR 4- and TLR 6-positive cells were significantly augmented for the MI group compared to the control group (p < 0.0167). Additionally, greenish corrosion particles found in the necrotic tissue suggested that metallic particles might release a certain level of locally toxic metallic ions in vivo.

Highlights

Due to electrochemical corrosion and mechanical wear, almost all metals and metallic alloys used for artificial joints will inevitably release metallic ions and wear particles in the human body, which causes periprosthetic biological reactions followed by aseptic implant loosening [1,2]
We provide some new insights to clarify the effects of metallic particles and metallic ions on Toll-like receptors (TLRs) expression in the present study, the exact patterns of TLR activation related to metallic byproducts still need to be further elucidated, which are the point of our further research
The results obtained in this investigation suggest that especially metallic wear particles result in a severe inflammatory response and high expression levels of surface TLRs

Summary

Introduction

Due to electrochemical corrosion and mechanical wear, almost all metals and metallic alloys used for artificial joints will inevitably release metallic ions and wear particles in the human body, which causes periprosthetic biological reactions followed by aseptic implant loosening [1,2]. Upregulated expression of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) are frequently detected in retrieved tissues associated with aseptic implant loosening [8,9] Based on this clinical evidence, it has been commonly accepted that wear particles and high levels of metallic ions cause sterile inflammatory reactions characterized by the continuous recruitment of immunocompetent cells, release of pro-inflammatory mediators, and sometimes formation of granulomatous tissues (pseudotumors) [10]. These adverse events will result in peri-implant osteolysis, followed by aseptic loosening in the mid/long term [2]. Whilst the general mechanism of sterile inflammation caused by wear particles and metallic ions has been established as described above, some detailed issues, such as the bioactive difference caused by between metallic particles and ions and exact patterns of the ligand-receptor recognition related to metallic particles and ions, remain controversial [11,12,13]

Methods

Discussion

Conclusion