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Inflammation Research

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01-07-2009 | Original Research Paper

Inhibitory effects of erythromycin on wear debris-induced VEGF/Flt-1 gene production and osteolysis

Authors: David C. Markel, Renwen Zhang, Tong Shi, Monica Hawkins, Weiping Ren

Published in: Inflammation Research | Issue 7/2009

Abstract

Objectives

A highly vascularized and inflammatory periprosthetic tissue augments the progress of aseptic loosening, a major clinical problem after total joint replacement. The purpose of this study is to investigate the effect of erythromycin (EM) on ultra high molecular weight polyethylene (UHMWPE) particle-induced VEGF/VEGF receptor 1 (Flt-1) gene production and inflammatory osteolysis in a mouse model.

Methods

UHMWPE particles were introduced into established air pouches on BALB/c mice, followed by implantation of calvaria bone from syngeneic littermates. EM treatment started 2 weeks after bone implantation (5 mg/kg day, i.p. injection). Mice without drug treatment as well as mice injected with saline alone were included. Pouch tissues were harvested 2 weeks after bone implantation. Expression of VEGF, Flt-1, RANKL, IL-1, TNF and CD68 was measured by immunostain and RT-PCR, and implanted bone resorption was analyzed by micro-CT (μCT).

Results

Exposure to UHMWPE induced pouch tissue inflammation, increase of VEGF/Flt-1 proteins, and increased bone resorption. EM treatment significantly improved UHMWPE particle-induced tissue inflammation, reduced VEGF/Flt-1 protein expression, and diminished the number of TRAP⁺ cells, as well as the implanted bone resorption.

Conclusion

This study demonstrated that EM inhibited VEGF and Flt-1 gene expression. The molecular mechanism of EM action on VEGF/Flt-1 signaling-mediated osteoclastogenesis warrants further investigation.

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Title: Inhibitory effects of erythromycin on wear debris-induced VEGF/Flt-1 gene production and osteolysis
Authors: David C. Markel
Renwen Zhang
Tong Shi
Monica Hawkins
Weiping Ren
Publication date: 01-07-2009
Publisher: SP Birkhäuser Verlag Basel
Published in: Inflammation Research / Issue 7/2009
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-009-0007-9

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Inhibitory effects of erythromycin on wear debris-induced VEGF/Flt-1 gene production and osteolysis

Abstract

Objectives

Methods

Results

Conclusion

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Abstract

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Conclusion

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