PMID- 34160894
OWN - NLM
STAT- MEDLINE
DCOM- 20220217
LR  - 20220217
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 25
IP  - 16
DP  - 2021 Aug
TI  - Bone marrow mesenchymal stem cell-derived exosomal miR-206 promotes osteoblast 
      proliferation and differentiation in osteoarthritis by reducing Elf3.
PG  - 7734-7745
LID - 10.1111/jcmm.16654 [doi]
AB  - MicroRNAs (miRNAs) serve as gene silencers involved in essential cell functions. 
      The role of miR-206 and E74-like factor 3 (Elf3) has been identified in 
      osteoarthritis (OA), while the effect of exosomal miR-206 from bone marrow 
      mesenchymal stem cells (BMSCs) in OA remains largely unknown. Thus, we aim to 
      explore the role of exosomal miR-206 from BMSCs in OA with the involvement of 
      Elf3. BMSCs and BMSC-derived exosomes (BMSC-exos) were obtained and identified. 
      OA mouse models were constructed by anterior cruciate ligament transection and 
      then treated with BMSC-exos or BMSC-exos containing miR-206 mimic/inhibitor. The 
      expression of miR-206, Elf3, inflammatory factors, osteocalcin (OCN) and bone 
      morphogenetic protein 2 (BMP2) in mouse femoral tissues was assessed. The 
      pathological changes in mouse femur tissues were observed. The mouse osteoblasts 
      were identified and treated with untransfected or transfected BMSC-exos, and 
      then, the expression of miR-206, Elf3, OCN and BMP2 was determined. The alkaline 
      phosphatase (ALP) activity, calcium deposition level, OCN secretion, 
      proliferation, apoptosis and cell cycle arrest in osteoblasts were measured. 
      MiR-206 was down-regulated while Elf3 was up-regulated in OA animal and cellular 
      models. Exosomal miR-206 ameliorated inflammation and increased expression of OCN 
      and BMP2 in mouse femoral tissues. Moreover, exosomal miR-206 promoted ALP 
      activity, calcium deposition level, OCN secretion and proliferation and inhibited 
      apoptosis in OA osteoblasts. Overexpressed Elf3 reversed miR-206 
      up-regulation-induced effects on OA osteoblasts. BMSC-derived exosomal miR-206 
      promotes proliferation and differentiation of osteoblasts in OA by reducing Elf3. 
      Our research may provide novel targets for OA treatment.
CI  - (c) 2021 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Huang, Yijiang
AU  - Huang Y
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Zhang, Xiumeng
AU  - Zhang X
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Zhan, Jingdi
AU  - Zhan J
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Yan, Zijiang
AU  - Yan Z
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Chen, Daosen
AU  - Chen D
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Xue, Xinghe
AU  - Xue X
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
FAU - Pan, Xiaoyun
AU  - Pan X
AUID- ORCID: 0000-0002-9133-9311
AD  - Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's 
      Hospital of Wenzhou Medical University, Wenzhou, China.
AD  - Key Laboratory of Orthopaedics of Zhejiang Province, Wenzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210623
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Elf3 protein, mouse)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn206 microRNA, mouse)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/*antagonists & inhibitors/metabolism
MH  - Disease Models, Animal
MH  - Exosomes/*genetics/metabolism
MH  - Mesenchymal Stem Cells/*cytology/metabolism
MH  - Mice
MH  - MicroRNAs/genetics/*pharmacology
MH  - Osteoarthritis/genetics/metabolism/pathology/*prevention & control
MH  - Osteoblasts/*cytology/metabolism
MH  - Transcription Factors/*antagonists & inhibitors/metabolism
PMC - PMC8358849
OTO - NOTNLM
OT  - E74-like factor 3
OT  - exosome
OT  - microRNA-206
OT  - osteoarthritis
OT  - osteoblasts
OT  - proliferation and differentiation
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2021/06/24 06:00
MHDA- 2022/02/19 06:00
PMCR- 2021/08/01
CRDT- 2021/06/23 12:42
PHST- 2021/04/28 00:00 [revised]
PHST- 2021/03/04 00:00 [received]
PHST- 2021/05/04 00:00 [accepted]
PHST- 2021/06/24 06:00 [pubmed]
PHST- 2022/02/19 06:00 [medline]
PHST- 2021/06/23 12:42 [entrez]
PHST- 2021/08/01 00:00 [pmc-release]
AID - JCMM16654 [pii]
AID - 10.1111/jcmm.16654 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2021 Aug;25(16):7734-7745. doi: 10.1111/jcmm.16654. Epub 2021 Jun 
      23.