Proteasome inhibition-enhanced fracture repair is associated with increased mesenchymal progenitor cells in mice.
PLoS One
; 17(2): e0263839, 2022.
Article
en En
| MEDLINE
| ID: mdl-35213543
ABSTRACT
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.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fracturas de la Tibia
/
Curación de Fractura
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Complejo de la Endopetidasa Proteasomal
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Proliferación Celular
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Células Madre Mesenquimatosas
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Inhibidores de Proteasoma
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Bortezomib
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2022
Tipo del documento:
Article