Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid

Sci Rep. 2021 Oct 1;11(1):19535. doi: 10.1038/s41598-021-98713-2.

Abstract

This study investigated the role 5-lypoxigenase (5-LO) on alveolar socket healing in aged female mice treated with zoledronic acid (ZL). Forty 129/Sv female mice (64-68 weeks old), 20 wild type (WT) and 20 5-LO knockout (5LOKO) were equally distributed according to ZL treatment: WT Control, WT ZL, 5LOKO Control, and 5LOKO ZL. ZL groups were treated with an intraperitoneal injection of 250 µg/Kg of ZL, while controls were treated with saline. Treatments were administered once a week, starting four weeks before surgery for tooth extraction and until 7 and 21 days post-surgery. Mice were euthanized for a comprehensive microscopic analysis (microCT, histomorphometry and immunohistochemistry). WT ZL mice presented intense inflammatory infiltrate (7 days), delayed bone formation (21 days), reduced collagenous matrix quality, and a deficiency in Runx-2 + , TRAP + , and macrophages as compared to controls. 5LOKO ZL animals presented decreased number of Runx-2 + cells in comparison to 5LOKO Control at 7 days, but no major changes in bone healing as compared to WT or 5LOKO mice at 21 days. The knockout of 5LO favored intramembranous bone healing in aged female mice, with a direct impact on inflammatory response and bone metabolism on the development of ONJ-like lesions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Arachidonate 5-Lipoxygenase / deficiency*
  • Arachidonate 5-Lipoxygenase / genetics
  • Biomarkers
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Tooth Extraction / adverse effects
  • Tooth Extraction / methods
  • Tooth Socket / diagnostic imaging
  • Tooth Socket / drug effects*
  • Tooth Socket / pathology
  • Treatment Outcome
  • Wound Healing / drug effects*
  • X-Ray Microtomography
  • Zoledronic Acid / administration & dosage*

Substances

  • Biomarkers
  • Zoledronic Acid
  • Arachidonate 5-Lipoxygenase