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Effect of cobalt and chromium ions on MMP-1, TIMP-1, and TNF-α gene expression in human U937 macrophages: A role for tyrosine kinases

Paper ID Volume ID Publish Year Pages File Format Full-Text
11063 716 2005 7 PDF Available
Title
Effect of cobalt and chromium ions on MMP-1, TIMP-1, and TNF-α gene expression in human U937 macrophages: A role for tyrosine kinases
Abstract

Previous reports have suggested that the imbalance of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) activity may contribute to prosthetic loosening. However, the mechanisms controlling these enzymes in the periprosthetic environment is unknown. We examined the effect of Co2+ and Cr3+ ions on the expression of genes encoding MMP-1, one of the principal proteinases capable of degrading native fibrillar collagens in the extracellular matrix (ECM), its inhibitor TIMP-1, and TNF-α, a cytokine that plays a central role in the induction of implant osteolysis. Human U937 macrophages were incubated in suspension or on phosphorylcholine (PC)-polymer coated surfaces for 24 h with Co2+ and Cr3+ ions. The level of mRNAs was determined by reverse transcription-polymerase chain reaction (RT–PCR). Results show that both Co2+ and Cr3+ ions induce the expression of MMP-1, TIMP-1, and TNF-α mRNA in a dose-dependent manner in cell suspensions. Tyrosine kinase inhibitors have different effects on these stimulatory effects. Indeed, genistein has only partial inhibitory effect on MMP-1 and TIMP-1, with even less effect on TNF-α expression. In contrast, herbimycin A completely blocks MMP-1 and TNF-α while partially inhibiting TIMP-1. However, Co2+ and Cr3+ ions had no effect on the expression of MMP-1 and TIMP-1 in macrophages cultured on the PC-polymer, suggesting that the attachment of U937 macrophages to the PC-polymer surfaces may modify their gene expression. In fact, MMP-1 and TIMP-1 seems to be constitutively up-regulated in this condition. However, the effect of Co2+ and Cr3+ ions on macrophages cultured on PC-polymer coated surfaces is similar to what was observed in suspension. Together, these findings indicate that activation of MMP-1, TIMP-1, and TNF-α by Co2+ and Cr3+ ions is regulated by tyrosine kinases.

Keywords
Cell adhesion; Hip replacement prosthesis; Macrophage; Matrix metalloproteinase; Metal ions; Phosphorylcholine
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Effect of cobalt and chromium ions on MMP-1, TIMP-1, and TNF-α gene expression in human U937 macrophages: A role for tyrosine kinases
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 26, Issue 28, October 2005, Pages 5587–5593
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us