Original Research Paper

Inflammation Research

, 58:413

First online:

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

  • David C. MarkelAffiliated withDepartment of Orthopaedic Surgery, Wayne State University
  • , Renwen ZhangAffiliated withStryker Company
  • , Tong ShiAffiliated withDepartment of Biomedical Engineering, Wayne State University
  • , Monica HawkinsAffiliated withStryker Company
  • , Weiping RenAffiliated withDepartment of Biomedical Engineering, Wayne State University Email author 

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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.


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).


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.


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.


VEGF Osteolysis Osteoclastogenesis Erythromycin Animal model Wear debris