Periprosthetic osteolysis: characterizing the innate immune response to titanium wear-particles
AuthorsSt. Pierre, Christine A.
Ayers, David C.
Kurt-Jones, Evelyn A.
Finberg, Robert W.
UMass Chan AffiliationsDepartment of Orthopedics and Physical Rehabilitation
Department of Medicine
Document TypeJournal Article
Arthroplasty, Replacement, Hip
Mice, Inbred C57BL
Rehabilitation and Therapy
MetadataShow full item record
AbstractOsteolysis 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.
SourceJ Orthop Res. 2010 Nov;28(11):1418-24. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/42937
Related ResourcesLink to Article in PubMed