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,...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Hengwei, Li, Xing, Liu, Jiatong, Lin, Xi, Pei, Lingpeng, Boyce, Brendan F., Xing, Lianping
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