PMID- 33510944
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210130
IS  - 2162-2531 (Print)
IS  - 2162-2531 (Electronic)
IS  - 2162-2531 (Linking)
VI  - 23
DP  - 2021 Mar 5
TI  - Exosomal miR-365a-5p derived from HUC-MSCs regulates osteogenesis in GIONFH 
      through the Hippo signaling pathway.
PG  - 565-576
LID - 10.1016/j.omtn.2020.12.006 [doi]
AB  - The pathogenesis of glucocorticoid (GC)-induced osteonecrosis of the femoral head 
      (GIONFH) is still disputed, and abnormal bone metabolism caused by GCs may be an 
      important factor. In vitro, Cell Counting Kit-8 (CCK-8) and 
      5-ethynyl-2'-deoxyuridine (EdU) staining were used to evaluate cellular 
      proliferation, and western blotting was used to investigate osteogenesis. 
      In vivo, we used micro-computed tomography (micro-CT), H&E staining, Masson 
      staining, and immunohistochemistry (IHC) analysis to evaluate the impact of 
      exosomes. In addition, the mechanism by which exosomes regulate osteogenesis 
      through the miR-365a-5p/Hippo signaling pathway was investigated using RNA 
      sequencing (RNA-seq), luciferase reporter assays, fluorescence in situ 
      hybridization (FISH), and western blotting. The results of western blotting 
      verified that the relevant genes in osteogenesis, including BMP2, Sp7, and Runx2, 
      were upregulated. RNA-seq and qPCR of the exosome and Dex-treated exosome groups 
      showed that miR-365a-5p was upregulated in the exosome group. Furthermore, we 
      verified that miR-365a-5p promoted osteogenesis by targeting SAV1. Additional 
      in vivo experiments revealed that exosomes prevented GIONFH in a rat model, as 
      shown by micro-CT scanning and histological and IHC analysis. We concluded that 
      exosomal miR-365a-5p was effective in promoting osteogenesis and preventing the 
      development of GIONFH via activation of the Hippo signaling pathway in rats.
CI  - (c) 2020 The Author(s).
FAU - Kuang, Ming-Jie
AU  - Kuang MJ
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
FAU - Zhang, Kai-Hui
AU  - Zhang KH
AD  - Department of Orthopedics, Tianjin Hospital, Tianjin 300211, China.
FAU - Qiu, Jie
AU  - Qiu J
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
FAU - Wang, An-Bang
AU  - Wang AB
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
FAU - Che, Wen-Wen
AU  - Che WW
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
FAU - Li, Xiao-Ming
AU  - Li XM
AD  - Department of Orthopedics, Traditional Chinese Medicine-Western Medicine Hospital 
      of Cangzhou City, Hebei Province 061000, China.
FAU - Shi, Dong-Li
AU  - Shi DL
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
FAU - Wang, Da-Chuan
AU  - Wang DC
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong 250014, China.
LA  - eng
PT  - Journal Article
DEP - 20201210
PL  - United States
TA  - Mol Ther Nucleic Acids
JT  - Molecular therapy. Nucleic acids
JID - 101581621
PMC - PMC7810916
OTO - NOTNLM
OT  - GIONFH
OT  - HUC-MSCs
OT  - Hippo signaling pathway
OT  - exosomes
OT  - osteogenesis
COIS- The authors declare no competing interests.
EDAT- 2021/01/30 06:00
MHDA- 2021/01/30 06:01
PMCR- 2020/12/10
CRDT- 2021/01/29 05:56
PHST- 2020/02/11 00:00 [received]
PHST- 2020/12/02 00:00 [accepted]
PHST- 2021/01/29 05:56 [entrez]
PHST- 2021/01/30 06:00 [pubmed]
PHST- 2021/01/30 06:01 [medline]
PHST- 2020/12/10 00:00 [pmc-release]
AID - S2162-2531(20)30387-5 [pii]
AID - 10.1016/j.omtn.2020.12.006 [doi]
PST - epublish
SO  - Mol Ther Nucleic Acids. 2020 Dec 10;23:565-576. doi: 10.1016/j.omtn.2020.12.006. 
      eCollection 2021 Mar 5.