Inflammation Research

, 58:413

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

  • David C. Markel
  • Renwen Zhang
  • Tong Shi
  • Monica Hawkins
  • Weiping Ren
Original Research Paper

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.

Keywords

VEGF Osteolysis Osteoclastogenesis Erythromycin Animal model Wear debris 

Abbreviations

VEGF

Vascular endothelial growth factor

EM

Erythromycin

Flt-1

VEGF receptor I

FLK

VEGF receptor II

RANK

Receptor activator of NF-κB

RANKL

RANK ligand

TNF

Tumor necrosis factor

IL-1

Interleukin-1

TRAP

Tartrate-resistant acid phosphatase

AL

Aseptic loosening

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Copyright information

© Birkhäuser Verlag, Basel/Switzerland 2009

Authors and Affiliations

  • David C. Markel
    • 1
  • Renwen Zhang
    • 3
  • Tong Shi
    • 2
  • Monica Hawkins
    • 3
  • Weiping Ren
    • 2
  1. 1.Department of Orthopaedic SurgeryWayne State UniversityDetroitUSA
  2. 2.Department of Biomedical EngineeringWayne State UniversityDetroitUSA
  3. 3.Stryker CompanyRutherfordUSA

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