Abstract

Background. Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. Questions/Purposes. The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. Methods. MC3T3 cells were pretreated with EM (0–10 μg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. Results. We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF-κB gene expression. Conclusions. These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles.

Highlights

  • Aseptic loosening (AL) is a major complication of total joint replacement (TJR) [1]

  • Addition of PMMA particles (1 mg/mL) to MC3T3 cells in nonosteogenic culture resulted in a time-dependent increase in lactate dehydrogenase (LDH) release over a 72 h period, compared with untreated cells

  • Activated macrophages and enhanced osteoclast activity are integral elements underlying bone destruction in periprosthetic osteolysis [18, 19], the effects of wear particles on osteoblastic cells significantly reduce the replacement of bone at the prosthetic interface [3]

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Summary

Introduction

Aseptic loosening (AL) is a major complication of total joint replacement (TJR) [1]. AL primarily results from a biological response of inflammatory cells and osteoblasts to wear particles [2, 3]. We found that EM inhibits wear particle-induced inflammatory osteolysis in a murine osteolysis model [11]. Encouraged by these laboratory findings, we designed a prospective clinical trial and revealed that oral EM (600 mg/daily) inhibits periprosthetic tissue inflammation in 32 AL patients who. The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles

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