M2 Macrophagy-derived exosomal miRNA-5106 induces bone mesenchymal stem cells towards osteoblastic fate by targeting salt-inducible kinase 2 and 3.
3' Untranslated Regions
Animals
Antagomirs
/ metabolism
Cell Differentiation
Coculture Techniques
Exosomes
/ metabolism
Femoral Fractures
/ pathology
Macrophages
/ cytology
Male
Mesenchymal Stem Cells
/ cytology
Mice
Mice, Inbred C57BL
MicroRNAs
/ antagonists & inhibitors
Osteoblasts
/ cytology
Osteocalcin
/ genetics
Osteogenesis
Protein Serine-Threonine Kinases
/ antagonists & inhibitors
RNA Interference
RNA, Small Interfering
/ metabolism
Exosome
Fracture
MiR-5106
Osteoblast
SIK2
SIK3
Journal
Journal of nanobiotechnology
ISSN: 1477-3155
Titre abrégé: J Nanobiotechnology
Pays: England
ID NLM: 101152208
Informations de publication
Date de publication:
28 Apr 2020
28 Apr 2020
Historique:
received:
18
03
2020
accepted:
21
04
2020
entrez:
30
4
2020
pubmed:
30
4
2020
medline:
6
11
2020
Statut:
epublish
Résumé
Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation. We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo. Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.
Sections du résumé
BACKGROUND
BACKGROUND
Osteoblast differentiation is a vital process for fracture healing, and exosomes are nanosized membrane vesicles that can deliver therapeutic drugs easily and safely. Macrophages participate in the regulation of various biological processes in vivo, and macrophage-derived exosomes (MD-Exos) have recently been a topic of increasing research interest. However, few study has explored the link between MD-Exos and osteoblast differentiation. Herein, we sought to identify miRNAs differentially expressed between M1 and M2 macrophage-derived exosomes, and to evaluate their roles in the context of osteoblast differentiation.
RESULTS
RESULTS
We found that microRNA-5106 (miR-5106) was significantly overexpressed in M2 macrophage-derived exosomes (M2D-Exos), while its expression was decreased in M1 macrophage-derived exosomes (M1D-Exos), and we found that this exosomal miRNA can induce bone mesenchymal stem cell (BMSC) osteogenic differentiation via directly targeting the Salt-inducible kinase 2 and 3 (SIK2 and SIK3) genes. In addition, the local injection of both a miR-5106 agonist or M2D-Exos to fracture sites was sufficient to accelerate healing in vivo.
CONCLUSIONS
CONCLUSIONS
Our study demonstrates that miR-5106 is highly enriched in M2D-Exos, and that it can be transferred to BMSCs wherein it targets SIK2 and SIK3 genes to promote osteoblast differentiation.
Identifiants
pubmed: 32345321
doi: 10.1186/s12951-020-00622-5
pii: 10.1186/s12951-020-00622-5
pmc: PMC7189726
doi:
Substances chimiques
3' Untranslated Regions
0
Antagomirs
0
MicroRNAs
0
RNA, Small Interfering
0
Osteocalcin
104982-03-8
salt-inducible kinase-2, mouse
EC 2.7.1.-
Protein Serine-Threonine Kinases
EC 2.7.11.1
SIK3 protein, mouse
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
66Subventions
Organisme : National Natural Science Foundation of China
ID : 81772345
Organisme : National Health and Family Planning Commission of the People's Republic of China
ID : No. ZX-01-018
Organisme : National Health and Family Planning Commission of the People's Republic of China
ID : ZX-01-C2106153
Organisme : Ministry of Science and Technology of the People's Republic of China
ID : 2018YFC2001502
Organisme : Ministry of Science and Technology of the People's Republic of China
ID : 2018YFB1105705
Commentaires et corrections
Type : ErratumIn
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