PMID- 33463060
OWN - NLM
STAT- MEDLINE
DCOM- 20211203
LR  - 20240330
IS  - 2001-1326 (Print)
IS  - 2001-1326 (Electronic)
IS  - 2001-1326 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jan
TI  - The umbilical cord mesenchymal stem cell-derived exosomal lncRNA H19 improves 
      osteochondral activity through miR-29b-3p/FoxO3 axis.
PG  - e255
LID - 10.1002/ctm2.255 [doi]
LID - e255
AB  - BACKGROUND: Our previous study revealed that the exosomal lncRNA H19 derived from 
      umbilical cord mesenchymal stem cells (UMSCs) plays a pivotal role in 
      osteochondral regeneration. In this study, we investigated whether the exosomal 
      lncRNA H19 could act as a competing endogenous RNA (ceRNA) to potentiate 
      osteochondral activity in chondrocytes. METHODS: Dual-luciferase reporter assay, 
      RNA pull-down, RNA immunoprecipitation (RIP), and fluorescence in situ 
      hybridization (FISH) were carried to verify the interaction between miR-29b-3p 
      and both lncRNA H19 and the target mRNA FoxO3. Chondrocytes were treated with 
      UMSC-derived exosomes, which highly expressing lncRNA H19 expression, followed by 
      apoptosis, migration, senescence, and matrix secretion assessments. An in vivo SD 
      rat cartilage defect model was carried out to explore the role and mechanism of 
      lncRNA H19/miR-29b-3p. RESULTS: UMSCs were successfully identified, and exosomes 
      were successfully extracted. Exosomes exhibited the ability to transfer lncRNA 
      H19 to chondrocytes. Mechanistically, exosomal lncRNA H19 potentiated 
      osteochondral activity by acting as a competing endogenous sponge of miR-29b-3p, 
      and miR-29b-3p directly targeted FoxO3. Intra-articular injection of exosomes 
      overexpressing lncRNA H19 could promote sustained cartilage repair; however, this 
      effect could be undermined by miR-29b-3p agomir. CONCLUSIONS: Our study revealed 
      a significant role in the development of strategies against cartilage defects for 
      UMSC-derived exosomes that overexpress lncRNA H19. Exosomal H19 was found to 
      promote chondrocyte migration, matrix secretion, apoptosis suppression, as well 
      as senescence suppression, both in vitro and in vivo. The specific mechanism lies 
      in the fact that exosomal H19 acts as a ceRNA against miR-29b-3p to upregulate 
      FoxO3 in chondrocytes.
CI  - (c) 2021 The Authors. Clinical and Translational Medicine published by John Wiley & 
      Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
FAU - Yan, Litao
AU  - Yan L
AD  - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, PR China.
FAU - Liu, Gejun
AU  - Liu G
AD  - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, PR China.
FAU - Wu, Xing
AU  - Wu X
AUID- ORCID: 0000-0002-5842-7555
AD  - Department of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Clin Transl Med
JT  - Clinical and translational medicine
JID - 101597971
RN  - 0 (FOXO3 protein, rat)
RN  - 0 (Forkhead Box Protein O3)
RN  - 0 (H19 long non-coding RNA)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
MH  - Animals
MH  - Cells, Cultured
MH  - Exosomes/*metabolism
MH  - Female
MH  - Forkhead Box Protein O3/*metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Mesenchymal Stem Cells/*metabolism
MH  - MicroRNAs/*metabolism
MH  - Osteocytes/*metabolism
MH  - RNA, Long Noncoding/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
MH  - Umbilical Cord/*cytology
PMC - PMC7805401
OTO - NOTNLM
OT  - chondrocytes
OT  - exosomes
OT  - long noncoding RNA
OT  - umbilical cord mesenchymal stem cells
COIS- The authors declare that there is no conflict of interest.
EDAT- 2021/01/20 06:00
MHDA- 2021/01/20 06:01
PMCR- 2021/01/13
CRDT- 2021/01/19 06:05
PHST- 2020/10/08 00:00 [received]
PHST- 2020/11/07 00:00 [revised]
PHST- 2020/12/06 00:00 [accepted]
PHST- 2021/01/19 06:05 [entrez]
PHST- 2021/01/20 06:00 [pubmed]
PHST- 2021/01/20 06:01 [medline]
PHST- 2021/01/13 00:00 [pmc-release]
AID - CTM2255 [pii]
AID - 10.1002/ctm2.255 [doi]
PST - ppublish
SO  - Clin Transl Med. 2021 Jan;11(1):e255. doi: 10.1002/ctm2.255.