PMID- 37181002
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230516
IS  - 1948-0210 (Print)
IS  - 1948-0210 (Electronic)
IS  - 1948-0210 (Linking)
VI  - 15
IP  - 4
DP  - 2023 Apr 26
TI  - Bone marrow mesenchymal stem cell-derived exosomal microRNAs target PI3K/Akt 
      signaling pathway to promote the activation of fibroblasts.
PG  - 248-267
LID - 10.4252/wjsc.v15.i4.248 [doi]
AB  - BACKGROUND: Fibroblast plays a major role in tendon-bone healing. Exosomes 
      derived from bone marrow mesenchymal stem cells (BMSCs) can activate fibroblasts 
      and promote tendon-bone healing via the contained microRNAs (miRNAs). However, 
      the underlying mechanism is not comprehensively understood. Herein, this study 
      aimed to identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets, 
      and to verify their effects as well as mechanisms on fibroblasts. AIM: To 
      identify overlapped BMSC-derived exosomal miRNAs in three GSE datasets and verify 
      their effects as well as mechanisms on fibroblasts. METHODS: BMSC-derived 
      exosomal miRNAs data (GSE71241, GSE153752, and GSE85341) were downloaded from the 
      Gene Expression Omnibus (GEO) database. The candidate miRNAs were obtained by the 
      intersection of three data sets. TargetScan was used to predict potential target 
      genes for the candidate miRNAs. Functional and pathway analyses were conducted 
      using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) 
      databases, respectively, by processing data with the Metascape. Highly 
      interconnected genes in the protein-protein interaction (PPI) network were 
      analyzed using Cytoscape software. Bromodeoxyuridine, wound healing assay, 
      collagen contraction assay and the expression of COL I and alpha-smooth muscle actin 
      positive were applied to investigate the cell proliferation, migration and 
      collagen synthesis. Quantitative real-time reverse transcription polymerase chain 
      reaction was applied to determine the cell fibroblastic, tenogenic, and 
      chondrogenic potential. RESULTS: Bioinformatics analyses found two BMSC-derived 
      exosomal miRNAs, has-miR-144-3p and has-miR-23b-3p, were overlapped in three GSE 
      datasets. PPI network analysis and functional enrichment analyses in the GO and 
      KEGG databases indicated that both miRNAs regulated the PI3K/Akt signaling 
      pathway by targeting phosphatase and tensin homolog (PTEN). In vitro experiments 
      confirmed that miR-144-3p and miR-23b-3p stimulated proliferation, migration and 
      collagen synthesis of NIH3T3 fibroblasts. Interfering with PTEN affected the 
      phosphorylation of Akt and thus activated fibroblasts. Inhibition of PTEN also 
      promoted the fibroblastic, tenogenic, and chondrogenic potential of NIH3T3 
      fibroblasts. CONCLUSION: BMSC-derived exosomes promote fibroblast activation 
      possibly through the PTEN and PI3K/Akt signaling pathways, which may serve as 
      potential targets to further promote tendon-bone healing.
CI  - (c)The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Li, Fang-Qi
AU  - Li FQ
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China.
FAU - Chen, Wen-Bo
AU  - Chen WB
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China.
FAU - Luo, Zhi-Wen
AU  - Luo ZW
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China.
FAU - Chen, Yi-Sheng
AU  - Chen YS
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China.
FAU - Sun, Ya-Ying
AU  - Sun YY
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China.
FAU - Su, Xiao-Ping
AU  - Su XP
AD  - Guangxi Key Laboratory of Oral and Maxillofacial Rehabilitation and 
      Reconstruction, Guangxi Medical University, Nanning 530021, Guangxi Zhuang 
      Autonomous Region, China.
FAU - Sun, Jun-Ming
AU  - Sun JM
AD  - Laboratory Animal Center, Guangxi Medical University, Nanning 530021, Guangxi 
      Zhuang Autonomous Region, China.
FAU - Chen, Shi-Yi
AU  - Chen SY
AD  - Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai 
      200040, China. cshiyi@163.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Stem Cells
JT  - World journal of stem cells
JID - 101535826
PMC - PMC10173806
OTO - NOTNLM
OT  - Exosome
OT  - Fibroblast
OT  - Mesenchymal stem cell
OT  - MicroRNA
OT  - Tendon-bone healing
COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of 
      interest for this article.
EDAT- 2023/05/14 19:13
MHDA- 2023/05/14 19:14
PMCR- 2023/04/26
CRDT- 2023/05/14 12:13
PHST- 2022/11/23 00:00 [received]
PHST- 2023/01/19 00:00 [revised]
PHST- 2023/03/23 00:00 [accepted]
PHST- 2023/05/14 19:14 [medline]
PHST- 2023/05/14 19:13 [pubmed]
PHST- 2023/05/14 12:13 [entrez]
PHST- 2023/04/26 00:00 [pmc-release]
AID - 10.4252/wjsc.v15.i4.248 [doi]
PST - ppublish
SO  - World J Stem Cells. 2023 Apr 26;15(4):248-267. doi: 10.4252/wjsc.v15.i4.248.