Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid
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,...
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Nature Portfolio
2021-10-01
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Online Access: | https://doi.org/10.1038/s41598-021-98713-2 |
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author | 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 |
author_facet | 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 |
author_sort | Ramez H. Mahmoud |
collection | DOAJ |
description | 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. |
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spelling | doaj.art-c92b6c44f3f8470a9461da063e895e7e2022-12-21T19:28:01ZengNature PortfolioScientific Reports2045-23222021-10-0111111510.1038/s41598-021-98713-2Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acidRamez H. Mahmoud0Claudia C. Biguetti1Gustavo B. Simionato2Isabela C. Custódio3Raquel B. P. Silva4Marco A. H. Duarte5Leonardo P. Faverani6Edilson Ervolino7Walid D. Fakhouri8Mariza A. Matsumoto9Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP)Department of Bioengineering, University of Texas at DallasDepartment of Basic Sciences, School of Dentistry, São Paulo State University (UNESP)Department of Health Sciences, Centro Universitário Sagrado CoraçãoDepartment of Basic Sciences, School of Dentistry, São Paulo State University (UNESP)Bauru School of Dentistry, University of São Paulo, FOB-USPDepartment of Surgery, School of Dentistry, São Paulo State University (UNESP)Department of Basic Sciences, School of Dentistry, São Paulo State University (UNESP)Center for Craniofacial Research, University of Texas Health Science Center at Houston, School of DentistryDepartment of Basic Sciences, School of Dentistry, São Paulo State University (UNESP)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.https://doi.org/10.1038/s41598-021-98713-2 |
spellingShingle | 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 Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid Scientific Reports |
title | Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
title_full | Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
title_fullStr | Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
title_full_unstemmed | Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
title_short | Alveolar socket healing in 5-lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
title_sort | alveolar socket healing in 5 lipoxygenase knockout aged female mice treated or not with high dose of zoledronic acid |
url | https://doi.org/10.1038/s41598-021-98713-2 |
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