Wear particles cause aseptic loosening by stimulating macrophages to produce inflammatory cytokines. Recent studies indicate that Toll-like receptor 2 (TLR2) and TLR4 mediate macrophage responses to the wear particles [1–3]. TLR2 and TLR4 uniquely activate MyD88-dependent signaling via an additional adapter protein known as TIRAP/Mal [4]. Del Vescovo et al reported that three single nucleotide polymorphisms (SNPs) within the TIRAP/Mal gene associate with aseptic loosening in THA patients [5]. The goal of the current study was therefore to determine whether TIRAP/Mal mediates responses to orthopaedic wear particles. Immortalized wild type (WT) and TIRAP/Mal knockout (KO) murine macrophages (Mfs) were incubated in the presence or absence of titanium (Ti) particles (1 × 108 particles/cm2 [2]. Three types of particles were used as described previously [1,2]: Ti particles with adherent bacterial debris (38.3 Endotoxin Units/109 particles), endotoxin-free Ti particles (<0.1 EU/109 particles), and Ti particles with adherent lipopolysacharide (LPS, 32.8 EU/109 particles). TNFa, IL-1b, and IL-6 mRNAs were measured by real-time PCR and the secreted cytokines were measured by ELISA. Particle-induced osteolysis in calvaria of TIRAP/Mal KO and WT mice was measured 7 days after particle implantation [1,2]. Introduction:
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