title: Simvastatin prevents the induction of interleukin-6 gene expression by titanium particles in human osteoblastic cells.
abstract: One of the most important complications of total joint arthroplasty is failure associated with periprosthetic osteolysis, a process mainly initiated by the biological response to wear-derived products from the biomaterials in service. The inflammatory mediator interleukin-6 (IL-6) plays a key role in the establishment and progression of aseptic loosening. Metal particles specifically up-regulate IL-6 production in bone-forming cells and implant-bone interfacial tissues. The use of statins has been recently associated with a significantly reduced risk of revision in patients that undergo total hip arthroplasty. We hypothesized that simvastatin (Simv) could modulate the osteoblastic response to titanium particles (Ti) by attenuating the production of IL-6. Pre-treatment of human osteoblastic cells with Simv down-regulated Ti particle-induced IL-6 gene expression at mRNA and protein levels. The effect of Simv on Ti-induced IL-6 production in osteoblastic cells could not be explained by inhibition of the internalization of metal particles. The mechanism involved in this down-regulation is based in the inhibition of the HMG-CoA/GGPP/RhoA/ROCK pathway, independently of Simv effects in the cholesterol synthesis. The cytokine-lowering property of Simv has been observed in Saos-2 cells and human primary osteoblasts (hOBs) exposed to Ti particles, and was further enhanced when hOBs were co-cultured with macrophages.
authors.affiliation: Unidad de Investigación, Hospital Universitario La Paz-IdiPAZ, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Vallés
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Alba
authors.initials: A
authors.lastname: Boré
authors.forename: Francisco
authors.initials: F
authors.lastname: Martín-Saavedra
authors.forename: Laura
authors.initials: L
authors.lastname: Saldaña
authors.forename: Nuria
authors.initials: N
authors.lastname: Vilaboa
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007124:Immunoenzyme Techniques; D015850:Interleukin-6 / Q000235:genetics*; D018613:Microscopy, Confocal; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019821:Simvastatin / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D015850:Interleukin-6; D019821:Simvastatin; D014025:Titanium