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

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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 1 2013

Fingerprint

Arachidonate 5-Lipoxygenase
Osteogenesis
A 78773
Lipoxygenase Inhibitors
Chondrogenesis
Drug Carriers
Fracture Healing
Bone Fractures
Bony Callus
Cyclooxygenase 2
Thigh
Histology
Animal Models
Inflammation
Lipids

All Science Journal Classification (ASJC) codes

  • Surgery
  • Orthopedics and Sports Medicine

Keywords

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

Cite this

Cottrell, J. A. ; Keshav, V. ; Mitchell, A. ; O'Connor, James. / Local inhibition of 5-lipoxygenase enhances bone formation in a rat model. In: Bone and Joint Research. 2013 ; Vol. 2, No. 2. pp. 41-50.
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Local inhibition of 5-lipoxygenase enhances bone formation in a rat model. / Cottrell, J. A.; Keshav, V.; Mitchell, A.; O'Connor, James.

In: Bone and Joint Research, Vol. 2, No. 2, 01.02.2013, p. 41-50.

Research output: Contribution to journalArticle

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AU - Mitchell, A.

AU - O'Connor, James

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