Local inhibition of 5-lipoxygenase enhances bone formation in a rat model

J. A. Cottrell, V. Keshav, A. Mitchell, J. P. O'Connor

Research output: Contribution to journalArticle

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Abstract

Objectives: Recent studies have shown that modulating inflammation-related lipid signalling after a bone fracture can accelerate healing in animal models. Specifically, decreasing 5-lipoxygenase (5-LO) activity during fracture healing increases cyclooxygenase-2 (COX-2) expression in the fracture callus, accelerates chondrogenesis and decreases healing time. In this study, we test the hypothesis that 5-LO inhibition will increase direct osteogenesis. Methods: Bilateral, unicortical femoral defects were used in rats to measure the effects of local 5-LO inhibition on direct osteogenesis. The defect sites were filled with a polycaprolactone (PCL) scaffold containing 5-LO inhibitor (A-79175) at three dose levels, scaffold with drug carrier, or scaffold only. Drug release was assessed in vitro. Osteogenesis was assessed by micro-CT and histology at two endpoints of ten and 30 days. Results: Using micro-CT, we found that A-79175, a 5-LO inhibitor, increased bone formation in an apparent dose-related manner. Conclusions: These results indicate that 5-LO inhibition could be used therapeutically to enhance treatments that require the direct formation of bone.

Original languageEnglish (US)
Pages (from-to)41-50
Number of pages10
JournalBone and Joint Research
Volume2
Issue number2
DOIs
StatePublished - Feb 2013

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All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Keywords

  • 5-lipoxygenase
  • A-79175
  • Bone formation
  • Bone regeneration
  • Femoral defect
  • Rat

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