PMID- 32057365
OWN - NLM
STAT- MEDLINE
DCOM- 20201020
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 524
IP  - 4
DP  - 2020 Apr 16
TI  - Human umbilical cord mesenchymal stem cell-derived exosomes act via the 
      miR-1263/Mob1/Hippo signaling pathway to prevent apoptosis in disuse 
      osteoporosis.
PG  - 883-889
LID - S0006-291X(20)30261-8 [pii]
LID - 10.1016/j.bbrc.2020.02.001 [doi]
AB  - Disuse osteoporosis (DOP) is a common complication resulting from the lack of or 
      disuse of mechanical loading and has been unsatisfactorily treated. We 
      hypothesized that exosomes derived from human umbilical cord mesenchymal stem 
      cells (HUCMSCs) could reduce bone marrow mesenchymal stem cell (BMSC) apoptosis 
      in rat DOP via the miR-1263/Mob1/Hippo signaling pathway. To evaluate the 
      function of exosomes derived from HUCMSCs (HUCMSC-Exos) in DOP, hind limb 
      unloading (HLU)-induced DOP rat models were prepared. In vitro, the proliferation 
      of BMSCs were evaluated using CCK-8 assays. Further, the apoptosis of BMSCs were 
      evaluated using annexin V-FITC assay and Western blots. In vivo, the protective 
      effects of HUCMSC-Exos were evaluated using HE staining and microCT analysis. The 
      underlying molecular mechanism of exosome action on BMSC apoptosis through the 
      miR-1263/Mob1/Hippo pathway was also investigated by high-throughput RNA 
      sequencing, luciferase reporter assays, RNA-pull down assays and Western blots. 
      The RNA-seq and q-PCR results showed that the level of miR-1263 was most abundant 
      among differentially expressed microRNAs. Exosomal miR-1263 could bind to the 
      3'untranslated region (3' UTR) of Mob1 and exert its function by directly 
      targeting Mob1 in recipient cells. The inhibition of Mob1 could activate YAP 
      expression. Hippo inhibition reversed the in vitro HLU-induced apoptotic effect 
      on BMSCs. The microCT and HE staining results indicated that HUCMSC-Exos 
      ameliorated DOP in vivo. Exosomes derived from HUCMSCs are effective at 
      inhibiting BMSC apoptosis and preventing rat DOP. This mechanism is mediated by 
      the miR-1263/Mob1/Hippo signaling pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Yang, Bao-Cheng
AU  - Yang BC
AD  - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 
      300052, People's Republic of China.
FAU - Kuang, Ming-Jie
AU  - Kuang MJ
AD  - Department of Orthopedics, The Provincial Hospital Affiliated to Shandong 
      University, Shandong, 250014, China.
FAU - Kang, Jia-Yu
AU  - Kang JY
AD  - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 
      300052, People's Republic of China.
FAU - Zhao, Jie
AU  - Zhao J
AD  - Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, People's Republic 
      of China.
FAU - Ma, Jian-Xiong
AU  - Ma JX
AD  - Department of Orthopedics, Tianjin Hospital, Tianjin, 300211, People's Republic 
      of China. Electronic address: mjx969@163.com.
FAU - Ma, Xin-Long
AU  - Ma XL
AD  - Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 
      300052, People's Republic of China. Electronic address: maxinlong8686@126.com.
LA  - eng
PT  - Journal Article
DEP - 20200210
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (MicroRNAs)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yap1 protein, rat)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/*genetics/metabolism
MH  - Animals
MH  - Apoptosis/genetics
MH  - Apoptosis Regulatory Proteins/genetics/metabolism
MH  - Cell Proliferation
MH  - Exosomes/genetics/metabolism/*transplantation
MH  - Gene Expression Regulation
MH  - Hindlimb Suspension/adverse effects/methods
MH  - Humans
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - MicroRNAs/*genetics/metabolism
MH  - Osteoporosis/etiology/genetics/pathology/*prevention & control
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Umbilical Cord/cytology/metabolism
MH  - YAP-Signaling Proteins
OTO - NOTNLM
OT  - Apoptosis
OT  - BMSCs
OT  - Disuse osteoporosis
OT  - Exosomes
OT  - Human umbilical cord mesenchymal stem cells
EDAT- 2020/02/15 06:00
MHDA- 2020/10/21 06:00
CRDT- 2020/02/15 06:00
PHST- 2020/01/10 00:00 [received]
PHST- 2020/02/01 00:00 [accepted]
PHST- 2020/02/15 06:00 [pubmed]
PHST- 2020/10/21 06:00 [medline]
PHST- 2020/02/15 06:00 [entrez]
AID - S0006-291X(20)30261-8 [pii]
AID - 10.1016/j.bbrc.2020.02.001 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2020 Apr 16;524(4):883-889. doi: 
      10.1016/j.bbrc.2020.02.001. Epub 2020 Feb 10.