Particle-Induced Osteolysis Is Mediated by TIRAP/Mal in Vitro and in Vivo: Dependence on Adherent Pathogen-Associated Molecular Patterns

The Journal of Bone and Joint Surgery. American Volume
Christopher P BechtelEdward M Greenfield

Abstract

Proinflammatory signaling by toll-like receptors (TLRs) likely contributes to biologic responses to wear particles causing aseptic loosening. We recently reported associations with aseptic loosening in patients with polymorphisms in the locus encoding an adapter protein specific for TLR-2 and TLR-4 known as toll/interleukin-1 receptor domain-containing adapter protein/MyD88 adapter-like (TIRAP/Mal). To directly examine the contribution of TIRAP/Mal, we tested the hypothesis that TIRAP/Mal deficiency reduces the activity of wear particles. Signaling by TLR-2 and TLR-4 through TIRAP/Mal can be activated by bacterial pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide or endogenous alarmins. To distinguish between those possibilities, we tested the hypothesis that the effects of TIRAP/Mal depend on the adherence of bacterial PAMPs to the particles. In vitro mRNA levels and secretion of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 were measured after incubating wild-type and TIRAP/Mal(-/-) macrophages in the presence or absence of titanium particles with adherent bacterial debris, so-called endotoxin-free particles, or particles with adherent lipopolysaccharide. In vivo osteolysis was measured after ...Continue Reading

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Citations

Dec 16, 2016·Journal of Biomedical Materials Research. Part a·Jukka PajarinenStuart B Goodman
Nov 17, 2017·Acta Orthopaedica·Jukka PajarinenBengt Mjöberg
Dec 6, 2017·The Journal of Bone and Joint Surgery. American Volume·Matthew J Allen
Aug 12, 2020·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Brian P FortEdward M Greenfield
Dec 7, 2019·Journal of Clinical Medicine·Stuart B Goodman, Jiri Gallo
Nov 2, 2019·Bioactive Materials·Joy-Anne N OliverDonghui Zhu

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