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Inhibition of miR-199b-5p reduces pathological alterations in osteoarthritis by potentially targeting Fzd6 and Gcnt2.

Tong Feng | Qi Zhang | Si-Hui Li | Yan-Ling Ping | Mu-Qiu Tian | Shuan-Hu Zhou | Xin Wang | Jun-Meng Wang | Fan-Rang Liang | Shu-Guang Yu | Qiao-Feng Wu
eLife | 2024

Osteoarthritis (OA) is a degenerative disease with a high prevalence in the elderly population, but our understanding of its mechanisms remains incomplete. Analysis of serum exosomal small RNA sequencing data from clinical patients and gene expression data from OA patient serum and cartilage obtained from the GEO database revealed a common dysregulated miRNA, miR-199b-5p. In vitro cell experiments demonstrated that miR-199b-5p inhibits chondrocyte vitality and promotes extracellular matrix degradation. Conversely, inhibition of miR-199b-5p under inflammatory conditions exhibited protective effects against damage. Local viral injection of miR-199b-5p into mice induced a decrease in pain threshold and OA-like changes. In an OA model, inhibition of miR-199b-5p alleviated the pathological progression of OA. Furthermore, bioinformatics analysis and experimental validation identified Gcnt2 and Fzd6 as potential target genes of MiR-199b-5p. Thus, these results indicated that MiR-199b-5p/Gcnt2 and Fzd6 axis might be a novel therapeutic target for the treatment of OA.

Pubmed ID: 38770735

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: National Key Research and Development Program of China,
    Id: 2019YFC1709000
  • Agency: National Key Research and Development Program of China,
    Id: 2022YFC3500703
  • Agency: Fund of Science and Technology Department of Sichuan Province,
    Id: 2022ZDZX0033
  • Agency: Xinglin Scholar Foundation of Chengdu University of Traditional Chinese Medicine,
    Id: QNTD2022003

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This is a list of tools and resources that we have found mentioned in this publication.


miRBase (tool)

RRID:SCR_003152

Central online repository for microRNA nomenclature, sequence data, annotation and target prediction.Collection of published miRNA sequences and annotation.

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PRISM (tool)

RRID:SCR_005375

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miRWalk (tool)

RRID:SCR_016509

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RRID:SCR_017354

Web tool for integrating human and mouse microRNAs in pathways.Pathway analysis web-server, providing statistics, while being able to accommodate advanced pipelines. Web server for assessment of miRNA regulatory roles and identification of controlled pathways. Supports all analyses for KEGG molecular pathways and Gene Ontology (GO) in seven species (Homo sapiens, Mus musculus, Rattus norvegicus, Drosophila melanogaster, Caenorhabditis elegans, Gallus gallus and Danio rerio).DIANA miRPath v.2.0 includes investigating combinatorial effect of microRNAs in pathways.DIANA-miRPath v3.0 includes deciphering microRNA function with experimental support.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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