title: Local inhibition of 5-lipoxygenase enhances bone formation in a rat model.
abstract: OBJECTIVE
  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.
authors.affiliation: University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Department of Biochemistry & Molecular Biology, Newark, New Jersey, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Cottrell
authors.forename: V
authors.initials: V
authors.lastname: Keshav
authors.forename: A
authors.initials: A
authors.lastname: Mitchell
authors.forename: J P
authors.initials: JP
authors.lastname: O'Connor
keywords: 5-lipoxygenase; A-79175; Bone formation; Bone regeneration; Femoral defect; Rat