Cargando…
Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice
The ubiquitin/proteasome system controls the stability of Runx2 and JunB, proteins essential for differentiation of mesenchymal progenitor/stem cells (MPCs) to osteoblasts. Local administration of proteasome inhibitor enhances bone fracture healing by accelerating endochondral ossification. However,...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880819/ https://www.ncbi.nlm.nih.gov/pubmed/35213543 http://dx.doi.org/10.1371/journal.pone.0263839 |
_version_ | 1784659316477788160 |
---|---|
author | Zhang, Hengwei Li, Xing Liu, Jiatong Lin, Xi Pei, Lingpeng Boyce, Brendan F. Xing, Lianping |
author_facet | Zhang, Hengwei Li, Xing Liu, Jiatong Lin, Xi Pei, Lingpeng Boyce, Brendan F. Xing, Lianping |
author_sort | Zhang, Hengwei |
collection | PubMed |
description | The ubiquitin/proteasome system controls the stability of Runx2 and JunB, proteins essential for differentiation of mesenchymal progenitor/stem cells (MPCs) to osteoblasts. Local administration of proteasome inhibitor enhances bone fracture healing by accelerating endochondral ossification. However, if a short-term administration of proteasome inhibitor enhances fracture repair and potential mechanisms involved have yet to be exploited. We hypothesize that injury activates the ubiquitin/proteasome system in callus, leading to elevated protein ubiquitination and degradation, decreased MPCs, and impaired fracture healing, which can be prevented by a short-term of proteasome inhibition. We used a tibial fracture model in Nestin-GFP reporter mice, in which a subgroup of MPCs are labeled by Nestin-GFP, to test our hypothesis. We found increased expression of ubiquitin E3 ligases and ubiquitinated proteins in callus tissues at the early phase of fracture repair. Proteasome inhibitor Bortezomib, given soon after fracture, enhanced fracture repair, which is accompanied by increased callus Nestin-GFP+ cells and their proliferation, and the expression of osteoblast-associated genes and Runx2 and JunB proteins. Thus, early treatment of fractures with Bortezomib could enhance the fracture repair by increasing the number and proliferation of MPCs. |
format | Online Article Text |
id | pubmed-8880819 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-88808192022-02-26 Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice Zhang, Hengwei Li, Xing Liu, Jiatong Lin, Xi Pei, Lingpeng Boyce, Brendan F. Xing, Lianping PLoS One Research Article The ubiquitin/proteasome system controls the stability of Runx2 and JunB, proteins essential for differentiation of mesenchymal progenitor/stem cells (MPCs) to osteoblasts. Local administration of proteasome inhibitor enhances bone fracture healing by accelerating endochondral ossification. However, if a short-term administration of proteasome inhibitor enhances fracture repair and potential mechanisms involved have yet to be exploited. We hypothesize that injury activates the ubiquitin/proteasome system in callus, leading to elevated protein ubiquitination and degradation, decreased MPCs, and impaired fracture healing, which can be prevented by a short-term of proteasome inhibition. We used a tibial fracture model in Nestin-GFP reporter mice, in which a subgroup of MPCs are labeled by Nestin-GFP, to test our hypothesis. We found increased expression of ubiquitin E3 ligases and ubiquitinated proteins in callus tissues at the early phase of fracture repair. Proteasome inhibitor Bortezomib, given soon after fracture, enhanced fracture repair, which is accompanied by increased callus Nestin-GFP+ cells and their proliferation, and the expression of osteoblast-associated genes and Runx2 and JunB proteins. Thus, early treatment of fractures with Bortezomib could enhance the fracture repair by increasing the number and proliferation of MPCs. Public Library of Science 2022-02-25 /pmc/articles/PMC8880819/ /pubmed/35213543 http://dx.doi.org/10.1371/journal.pone.0263839 Text en © 2022 Zhang et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Zhang, Hengwei Li, Xing Liu, Jiatong Lin, Xi Pei, Lingpeng Boyce, Brendan F. Xing, Lianping Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title | Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title_full | Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title_fullStr | Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title_full_unstemmed | Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title_short | Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
title_sort | proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880819/ https://www.ncbi.nlm.nih.gov/pubmed/35213543 http://dx.doi.org/10.1371/journal.pone.0263839 |
work_keys_str_mv | AT zhanghengwei proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT lixing proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT liujiatong proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT linxi proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT peilingpeng proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT boycebrendanf proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice AT xinglianping proteasomeinhibitionenhancedfracturerepairisassociatedwithincreasedmesenchymalprogenitorcellsinmice |