Cobalt ions induce chemokine secretion in primary human osteoblasts.
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.
Queally
J M
JM
UCD Clinical Research Centre, UCD School of Medicine & Medical Sciences, Mater University Hospital, Dublin, Ireland. josephqueally@gmail.com
Devitt
B M
BM
Butler
J S
JS
Malizia
A P
AP
Murray
D
D
Doran
P P
PP
O'Byrne
J M
JM
D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D003035:Cobalt / Q000633:toxicity*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D007477:Ions; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D010006:Osteoblasts / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010014:Osteolysis / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D007477:Ions; D012333:RNA, Messenger; D003035:Cobalt; D015232:Dinoprostone