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.
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ABSTRACT: Osteoarthritis and lesions to cartilage tissue are diseases that frequently result in impaired joint function and patient disability. The treatment of osteoarthritis, along with local bone defects and systemic skeletal diseases, remains a significant clinical challenge for orthopaedic surgeons. Several bone morphogenetic proteins (BMPs) are known to have osteoinductive effects, whereof BMP-2 and BMP-7 are already approved for clinical applications. There is growing evidence that the metabolism of bone as well as the cartilage damage associated with the above disease processes are strongly inter-related with the interactions of the inflammation-related pathways (in particular prostaglandin E(2) (PGE(2))) and osteogenesis (in particular bone morphogenetic protein-2 (BMP-2)). There is strong evidence that the pathways of prostaglandins and bone morphogenetic proteins are intertwined, and they have recently come into focus in several experimental and clinical studies. This paper focuses on PGE(2) and BMP-2 intertwining pathways in bone and cartilage metabolism, and summarizes the recent experimental and clinical data.Canadian Journal of Physiology and Pharmacology 11/2012; 90(11):1434-45. DOI:10.1139/y2012-123 · 1.55 Impact Factor
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ABSTRACT: Metal ion toxicity both locally and systemically following MoM hip replacements remains a concern. Cobalt ions have been shown to induce secretion of proinflammatory chemokines locally; however, little is known about their effect systemically. We investigated the in vitro effect of cobalt ions on a variety of cell lines by measuring production of the proinflammatory chemokines IL-8 and MCP-1. Renal, gastrointestinal, and respiratory epithelium and also neutrophils and monocytes were exposed to cobalt ions at 4, 12, 24, and 48 hours. We found that cobalt ions enhanced the secretion of IL-8 and MCP-1 in renal epithelial cells, gastric and colon epithelium, monocytes and neutrophils, and small airway epithelial cells but not in alveolar cells. Secretion of IL-8 and MCP-1 was markedly elevated in renal epithelium, where a 16-fold and 7-fold increase occurred compared to controls. There was a 6-fold and 4-fold increase in IL-8 and MCP-1 secretion in colon epithelium and a 4-fold and 3-fold increase in gastric epithelium. Small airway epithelial cells showed a maximum increase in secretion of 8-fold (IL-8) and of 4-fold (MCP-1). The increase in chemokine secretion observed in alveolar cells was moderate and did not reach statistical significance. Monocytes and neutrophils showed a 2.5-fold and 2-fold increase in IL-8 secretion and a 6-fold and 4-fold increase in MCP-1 secretion at 48 and 24 hours, respectively. These data demonstrate the potent bioactivity of cobalt ions in a variety of cell types and the potential to induce a proinflammatory response.Acta Orthopaedica 12/2010; 81(6):756-64. DOI:10.3109/17453674.2010.537806 · 2.45 Impact Factor