Increased Expression of Toll-like Receptors in Aseptic Loose Periprosthetic Tissues and Septic Synovial Membranes Around Total Hip Implants

Tamaki, Yasuhiro; Takakubo, Yuya; Goto, Kaoru; Hirayama, Tomoyuki; Sasaki, Kan; Konttinen, Yrjö T.; Goodman, Stuart B.; Takagi, Michiaki

doi:10.3899/jrheum.080390

Cited by 56 publications

(64 citation statements)

References 44 publications

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“…Multiple lines of evidence indicate that activation of TLRs is likely to be another factor that regulates the biologic reaction to wear particles. Consistent with this possibility, macrophages in periprosthetic tissues, like macrophages in other tissues, constitutively express a diverse array of TLRs [57,80,103]. It is intriguing that oxidized alkane polymers derived from UHMWPE particles can accumulate in periprosthetic tissue and can activate TLR1/TLR2 heterodimers but cannot activate TLR3 or TLR4 [64,65].…”

Section: Toll-like Receptorsmentioning

confidence: 93%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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Background Overwhelming evidence supports the concept that wear particles are the primary initiator of aseptic loosening of orthopaedic implants. It is likely, however, that other factors modulate the biologic response to wear particles. This review focuses on three potential other factors: genetic susceptibility, Toll-like receptors (TLRs), and bacterial pathogen-associated molecular patterns (PAMPs). Where Are We Now? Considerable evidence is emerging that both genetic susceptibility and TLR activation are important factors that modulate the biologic response to wear particles, but it remains controversial whether bacterial PAMPs also do so. Where Do We Need to Go? Detailed understanding of the roles of these other factors may lead to identification of novel therapeutic targets for patients with aseptic loosening. How Do We Get There? Highest priority should be given to polymorphism replication studies with large numbers of patients and studies to replicate the reported correlation between bacterial biofilms and the severity of aseptic loosening.

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Section: Toll-like Receptorsmentioning

confidence: 93%

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Greenfield

2014

Clin Orthop Relat Res

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“…[1][2][3][4][5][6][7] Toll-like receptors (TLRs) and nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) have been reported to contribute to the pathogenesis of osteolysis induced by implant wear particles. [8][9][10][11][12] Expression of TLR2, TLR4, TLR5, and TLR9 is increased in macrophages in aseptic periprosthetic tissues of loose implants. [8][9][10] These TLRs could respond to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), inducing inflammatory cytokines and evoking osteolysis around THA implants.…”

Section: Introductionmentioning

confidence: 99%

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Naganuma

Takakubo

Hirayama

et al. 2015

J Biomedical Materials Res

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Toll-like receptor 2 (TLR2) and nucleotide-binding and oligomerization domain-like receptors with a pyrin domain 3 (NLRP3) inflammasomes have been presumed to participate in the pathogenesis of aseptic implant loosening. The aim of this study is to analyze the cellular localization of TLR2 and NLRP3 inflammasomes in the periprosthetic tissue from aseptically loose hip implants as well as the expression of these molecules in macrophages stimulated in vitro with titanium particles (Ti) coated with lipoteichoic acid (LTA). Using immunohistochemistry, immunoreactivity of TLR2 and NLRP3 inflammasomes was found in macrophages within the foreign body granulomatosis. Using RAW264.7 cells, stimulation with Ti increased the messenger RNA (mRNA) levels of TLR2 and TNF-α. Stimulation with LTA-coated Ti enhanced mRNA levels of NLRP3 and IL-1β, whereas reinforced secretion of IL-1β was not detected in spite of marked release of TNF-α. Finally, the same cells with silenced Irak2, an adaptor protein in the TLR2 cascade, suppressed this NLRP3 upregulation. This study suggests that TLR2 and NLRP3 inflammasomes are factors involved in cross-talk mediating the foreign body type response to wear particles. In addition, discrepant behavior in the release between TNF-α and IL-1β release may explain the variable pathomechanisms of aseptic implant loosening without acute inflammatory reactions.

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“…To this end, numerous researchers have focused on improving existing methods for diagnosing infection (ie, preoperative and intraoperative cultures [2,3,16,27,46] and Gram stain [2,12,20,49], serum markers of inflammation [19,23,27], synovial white blood cell [WBC] count and polymorphonuclear [PMN] percentages [5,21,29,34,48], intraoperative frozen section [11,14,15,17,42] and preoperative tissue biopsy [32,36], and nuclear medicine…”

Section: Introductionmentioning

confidence: 99%

Mark B. Coventry Award: Synovial C-reactive Protein: A Prospective Evaluation of a Molecular Marker for Periprosthetic Knee Joint Infection

Parvızı

Jacovides

Adeli

et al. 2012

Clinical Orthopaedics &Amp; Related Research

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Background C-reactive protein (CRP) serum assays are a standard element of the diagnostic workup for periprosthetic joint infection (PJI). However, because CRP is a marker for systemic inflammation, this test is not specific to PJI. Questions/purposes Our purpose was to assess whether synovial fluid and serum assays alone could differentiate between infected and uninfected revision knee arthroplasties and to determine which of these methods had the greatest diagnostic accuracy. Methods We collected synovial fluid specimens from 66 patients undergoing revision total knee arthroplasty. Patients were judged uninfected or infected by standardized criteria. Synovial CRP levels were measured using an individual CRP assay (15 samples; 10 infected, five uninfected) and a multiplex immunoassay platform (59 samples; 25 infected, 34 uninfected). Results from preoperative standard serum CRP assays conducted were also collected (55 samples; 25 infected, 30 uninfected). Sensitivity, specificity, and receiver operating characteristic curve analyses were performed for each assay with a diagnosis of infection based on previously established criteria.Results Synovial CRP concentrations differed between infected and uninfected joints in the multiplex and serum analyses. The area under the curve was 0.84 for the individual assay, 0.91 for the multiplex assay, and 0.88 for the serum CRP assay. Sensitivity and specificity were 70.0% and 100.0% for the individual enzyme-linked immunosorbent assay, 84.0% and 97.1% for the multiplex assay, and 76.0% and 93.3% for the serum CRP assay. Conclusions An assay measuring CRP in synovial fluid may be more accurate in diagnosing PJI than the standard serum CRP assay. We believe such an assay holds promise as a new diagnostic marker for PJI.

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Increased Expression of Toll-like Receptors in Aseptic Loose Periprosthetic Tissues and Septic Synovial Membranes Around Total Hip Implants

Cited by 56 publications

References 44 publications

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Do Genetic Susceptibility, Toll-like Receptors, and Pathogen-associated Molecular Patterns Modulate the Effects of Wear?

Lipoteichoic acid modulates inflammatory response in macrophages after phagocytosis of titanium particles through Toll‐like receptor 2 cascade and inflammasomes

Mark B. Coventry Award: Synovial C-reactive Protein: A Prospective Evaluation of a Molecular Marker for Periprosthetic Knee Joint Infection

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