Cobalt ions induce chemokine secretion in primary human osteoblasts

UCD Clinical Research Centre, UCD School of Medicine & Medical Sciences, Mater University Hospital, Dublin, Ireland.
Journal of Orthopaedic Research (Impact Factor: 2.99). 07/2009; 27(7):855-64. DOI: 10.1002/jor.20837
Source: PubMed


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.

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    • "In particular, titanium wear particles were found to activate PGE 2 production in fibroblasts through a COX-2 dependent pathway (Bukata et al. 2004). Other investigations also demonstrated a pro-inflammatory response of human osteoblasts to cobalt ions, leading to increased secretion of chemokines including PGE 2 (Queally et al. 2009). A decrease in the secretion of alkaline phosphatase and in calcium deposition, markers of osteoblastic differentiation, was measured. "
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    • "These chemokines initiate the progression of an inflammatory response, which is governed to a large extent by the continued availability of infiltrating leukocytes that are recruited to the site of inflammatory injury. Previous studies have shown that cobalt ions lead to increased chemokine secretion in primary human osteoblasts with the potential to induce osteolysis by recruiting inflammatory leukocytes (Queally and Devitt et al. 2009). We hypothesized that cobalt ions have a similar pro-inflammatory effect on other systemic cell lines, thus potentially inducing an inflammatory condition or exacerbate an existing one. "
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