Periprosthetic osteolysis: characterizing the innate immune response to titanium wear-particles
Department of Medicine; Department of Orthopedics and Physical Rehabilitation
Medical Subject Headings
Animals; Arthroplasty, Replacement, Hip; Carrier Proteins; Cells, Cultured; Humans; Immunity, Innate; Interleukin-1; Macrophages; Mice; Mice, Inbred C57BL; Neutrophil Infiltration; Osteolysis; Titanium
Orthopedics | Rehabilitation and Therapy
Osteolysis of bone following total hip replacement is a major clinical problem. Examination of the areas surrounding failed implants has indicated an increase in the bone-resorption-inducing cytokine, interleukin 1beta (IL-1beta). NALP3, a NOD-like receptor protein located in the cytosol of macrophages, signals the cleavage of pro-IL-1beta into its mature, secreted form, IL-1beta. Here we showed that titanium particles stimulate the NALP3 inflammasome. We demonstrated that titanium induces IL-1beta secretion from macrophages. This response depended on the expression of components of the NALP3 inflammasome, including NALP3, ASC, and Caspase-1. We also showed that titanium particles trigger the recruitment of neutrophils and that this acute inflammatory response depends on the expression of the IL-1 receptor and IL-1alpha/beta. Moreover, administration of the IL-1 receptor antagonist (IL-1Ra) diminished neutrophil recruitment in response to titanium particles. Together, these results suggest that titanium particle-induced acute inflammation is due to activation of the NALP3 inflammasome, which leads to increased IL-1beta secretion and IL-1-associated signaling, including neutrophil recruitment. Efficacy of IL-1Ra treatment introduces the potential for antagonist-based therapies for implant osteolysis.
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Citation: J Orthop Res. 2010 Nov;28(11):1418-24. Link to article on publisher's site