A novel biologically hierarchical hydrogel with osteoblast precursor-targeting extracellular vesicles ameliorates bone loss in vivo via the sequential action of antagomiR-200b-3p and antagomiR-130b-3p.
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
revised:
10
01
2023
received:
03
12
2022
accepted:
02
02
2023
medline:
3
8
2023
pubmed:
15
2
2023
entrez:
14
2
2023
Statut:
ppublish
Résumé
Osteoporotic fracture is a major health problem plaguing the ageing society, and improving its treatment is an urgent challenge. How to ameliorate bone loss determines the recovery of such fractures. Extracellular vesicle (EV)-loaded hydrogel has the capacity to treat osteoporotic fractures due to its pro-osteogenic property. And balancing proliferation and maturation of osteoblast precursors (OBPs) is of great significance to avoid OBP depletion, which is lacking in current treatment. Based on osteoblastogenic miRNAs, this study aimed to explore the efficacies of the combination of hierarchical hydrogel and EVs altering functional miRNAs level in bone loss. Through bioinformatics analyses, we screened out proliferative gene-targeting miR-200b-3p and osteogenic gene-targeting miR-130b-3p. And antagomiR-200b-3p (ant-200b) enhanced OBP proliferation, and antagomiR-130b-3p (ant-130b) promoted OBP differentiation. After confirming the directional effect of Fibronectin (Fn1) on OBPs, we prepared OBP-targeting EVs. Furthermore, encapsulation of two antagomiRNAs in EVs enhanced the respective effect of ant-200b and ant-130b. Notably, hierarchically injectable hydrogel exerted an effective function in promoting the sequential delivery of EVs-200b and EVs-130b. Importantly, hierarchical hydrogel containing dual EVs effectively ameliorated bone loss. Overall, hierarchical hydrogel based on two antagomiRNAs effectively improves bone loss in vivo due to its role in promoting OBP proliferation and maturation sequentially.
Identifiants
pubmed: 36786008
doi: 10.1111/cpr.13426
pmc: PMC10392057
doi:
Substances chimiques
Antagomirs
0
Hydrogels
0
MicroRNAs
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13426Subventions
Organisme : Fujian Provincial Natural Science Foundation Projects
ID : 2020J011079
Organisme : Health Research Personnel Training Project of Fujian Provincial Health Commission
ID : 2019-CX-1
Organisme : Joint Fund Project for Science and Technology Innovation
ID : 2021Y9023
Organisme : Joint Project for Health and Education of Fujian Province
ID : 2019-WJ-01
Organisme : Major Scientific Research Project of Fujian Province
ID : 2021ZD01003
Organisme : Postdoctoral Science Foundation of China
ID : 2022M710702
Organisme : Postdoctoral start-up fund of Fujian Provincial Hospital
ID : 0080132201
Organisme : Science and Technology Planning Project of Fujian Province
ID : 2019J01173
Organisme : Startup Fund for Scientific Research of Fujian Medical University
ID : 2020QH2050
Informations de copyright
© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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