Erythromycin inhibits wear debris-induced osteoclastogenesis by modulation of murine macrophage NF-κB activity

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Abstract

Activation of nuclear factor kappa B (NF-κB) signaling in response to cell stimulation by wear debris may be critical in the (pathogenesis of aseptic loosening. Erythromycin (EM), a macrolide antibiotic, has been shown to effectively suppress some types of inflammatory reactions. In this study, we examined the effect of EM on wear debris-induced osteoclastic bone resorption in vitro. EM inhibited Ca+ release from neonatal calvaria co-cultured with conditioned medium from mouse RAW264.7 macrophages activated by wear debris. Inhibition of Ca+ release was associated with a decreased number of tartrate-resistant acid phosphatase (TRAP)-positive cells in cultured bones. To investigate the mechanism whereby EM inhibits bone-resorption, RAW cells were incubated with wear debris in the presence EM. Real time RT-CR analysis revealed that EM (5 μg/ml) significantly inhibited mRNA expression of NF-κB, cathepsin K (CPK , IL-1β and TNFα, but not RANK in RAW cells stimulated with wear debris. Furthermore, electrophoretic mobility-shift assay showed that EM (0.2 μg-5 μg/ml) could reduce DNA-binding activity of NF-κB in RAW cells stimulated with wear debris. The inhibition of inflammatory osteoclastogenesis by EM treatment was further confirmed by an osteoclast (OC) formation assay using primary cultures of mouse bone marrow progenitor cells stimulated with macrophage colony-stimulating factor and RANK ligand (RANKL). EM treatment (5 μg/ml) resulted in more than 70% reduction in multi-nucleated OC formation and 50% reduction of TRAP+ cells by bone marrow progenitor cells. Our findings support that EM suppresses wear debris-induced osteoclastic bone resorption by, at least, down-regulation of NF-κB signaling pathway. It appears that EM represents a potential therapeutic candidate for the treatment and prevention of aseptic loosening. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.

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APA

Ren, W., Li, X. H., Chen, B. D., & Wooley, P. H. (2004). Erythromycin inhibits wear debris-induced osteoclastogenesis by modulation of murine macrophage NF-κB activity. Journal of Orthopaedic Research, 22(1), 21–29. https://doi.org/10.1016/S0736-0266(03)00130-X

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