Cobalt ions induce chemokine secretion in primary human osteoblasts

Abstract

Chemokines are major regulators of the inflammatory response and have been shown to play an important role in periprosthetic osteolysis. Titanium particles have previously been shown to induce IL-8 and MCP-1 secretion in osteoblasts. These chemokines result in the chemotaxis and activation of neutrophils and macrophages, respectively. Despite a resurgence in the use of cobalt-chromium-molybdenum alloys in metal-on-metal arthroplasty, cobalt and chromium ion toxicity in the periprosthetic area has been insufficiently studied. In this study we investigate the in vitro effect of cobalt ions on primary human osteoblast activity. We demonstrate that cobalt ions rapidly induce the protein secretion of IL-8 and MCP-1 in primary human osteoblasts. This elevated chemokine secretion is preceded by an increase in the transcription of the corresponding chemokine gene. Using a Transwell migration chemotaxis assay we also demonstrate that the chemokines secreted are capable of inducing neutrophil and macrophage migration. Furthermore, cobalt ions significantly inhibit osteoblast function as demonstrated by reduced alkaline phosphatase activity and calcium deposition. In aggregate these data demonstrate that cobalt ions can activate transcription of the chemokine genes IL-8 and MCP-1 in primary human osteoblasts. Cobalt ions are not benign and may play an important role in the pathogenesis of osteolysis by suppressing osteoblast function and stimulating the production and secretion of chemokines that attract inflammatory and osteoclastic cells to the periprosthetic area. ß

Radiographically Undetectable Periprosthetic Osteolysis With ASR Implants

“…In vitro studies have demonstrated how higher cobalt ions concentrations inhibit primary human osteoblast and attract inflammatory and osteoclastic cells [13]. Elevated cobalt and chromium ions levels result in osteolytic reactions [12].…”

“…High cobalt and chromium concentrations have adverse effect on bone cells viability and osteoclast resorption [12,13]. Therefore, it should be logical to expect an increasing incidence of periprosthetic osteolysis around ASR implants of patients presenting high blood metal ion levels.…”

The Protective Effect of Bafilomycin A1 Against Cobalt Nanoparticle-Induced Cytotoxicity and Aseptic Inflammation in Macrophages In Vitro

“…MOM bearings made of a cobalt −chromium (CoCr) alloy generate a large amount of metal particles and ions in vivo [2]. Metal particles obtained from revisioned periprosthetic tissues were smaller than 50 nm, and the number of wear particles was 13-500 times higher than that seen in MOP bearings [4,5].…”

Peri-prosthetic tissue cells show osteogenic capacity to differentiate into the osteoblastic lineage

“…The few studies investigating their role in bone formation show that peri‐prosthetic tissue cells produce factors that suppress osteoblast function and induce production of inflammatory cytokines 12, 13. Moreover, wear particles and metal ions can directly affect osteoblasts by reducing type one collagen production14, 15 and decreasing alkaline phosphatase activity as well as calcium deposition 16. In addition, wear particles have been shown to decrease osteoblast proliferation,15, 17 change the phenotype of mature osteoblasts,18 and stimulate osteoblasts to secrete inflammatory cytokines 14, 15, 16, 19.…”

“…Moreover, wear particles and metal ions can directly affect osteoblasts by reducing type one collagen production14, 15 and decreasing alkaline phosphatase activity as well as calcium deposition 16. In addition, wear particles have been shown to decrease osteoblast proliferation,15, 17 change the phenotype of mature osteoblasts,18 and stimulate osteoblasts to secrete inflammatory cytokines 14, 15, 16, 19. Remarkably, one study revealed that cells from the peri‐prosthetic tissue produce several osteoblastic proteins themselves 20.…”