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

• Main Authors: Ramez H. Mahmoud, Claudia C. Biguetti, Gustavo B. Simionato, Isabela C. Custódio, Raquel B. P. Silva, Marco A. H. Duarte, Leonardo P. Faverani, Edilson Ervolino, Walid D. Fakhouri, Mariza A. Matsumoto
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-10-01
• Series: Scientific Reports
• Online Access: https://doi.org/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.