Synovial fibroblast-derived exosomal microRNA-106b suppresses chondrocyte proliferation and migration in rheumatoid arthritis via down-regulation of PDK4.

Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte
Dan LiuGuoqing Li

Abstract

Fibroblast-derived exosomes have been reported to transfer microRNAs to recipient cells, where they regulate target gene expression, which is of interest for understanding the basic biology of inflammation, tissue homeostasis, and development of therapeutic approaches. Initial microarray-based analysis carried out in this study identified the rheumatoid arthritis (RA)-related differentially expressed gene pyruvate dehydrogenase kinase 4 (PDK4). Subsequently, the upstream regulatory microRNA-106b (miR-106b) of PDK4 was predicted with bioinformatic analyses. A collagen-induced arthritis (CIA)-induced mouse model was established, and exosomes were isolated from synovial fibroblasts (SFs) and transferred into chondrocytes to identify the role of exosomes in rheumatoid arthritis (RA). We found that PDK4 was poorly expressed in RA cartilage tissues and chondrocytes, while miR-106b was highly expressed in RA SFs and SF-derived exosomes. Notably, PDK4 was confirmed as a target gene of miR-106b. Over-expression of PDK4 promoted the proliferation and migration abilities of chondrocytes and inhibited their apoptosis as well as affected the receptor activator of nuclear factor kappa B ligand (RANKL)/RANK/osteoprotegerin (OPG) system. Meanw...Continue Reading

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Citations

May 20, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chenggui MiaoJinling Huang
Jul 27, 2021·Frontiers in Immunology·Jie HuangChao Liang
Oct 1, 2021·Nature Reviews. Rheumatology·Shabana A AliMohit Kapoor

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Datasets Mentioned

BETA
GSE77298
GSE97779

Methods Mentioned

BETA
transmission electron microscopy
transfection
Assay
flow cytometry

Software Mentioned

SPSS
TargetScan
limma
DIANA
Cytoscape
R language
DiGSeE
Affy package

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