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Decreased miR-214-3p activates NF-κB pathway and aggravates osteoarthritis progression

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Cao, Y, Tang, S, Nie, X, Zhou, Z, Ruan, G, Han, W, Zhu, Z and Ding, C ORCID: 0000-0002-9479-730X 2021 , 'Decreased miR-214-3p activates NF-κB pathway and aggravates osteoarthritis progression' , EBioMedicine, vol. 65 , pp. 1-11 , doi: 10.1016/j.ebiom.2021.103283.

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Abstract

Background:Osteoarthritis (OA), a disease with whole-joint damage and dysfunction, is the leading cause of disability worldwide. The progressive loss of hyaline cartilage extracellular matrix (ECM) is considered as its hallmark, but its exact pathogenesis needs to be further clarified. MicroRNA(miRNA) contributes to OA pathology and may help to identify novel biomarkers and therapies against OA. Here we identified miR-214–3p as an important regulator of OA.Methods:qRT-PCR and in situ hybridization were used to detect the expression level of miR-214–3p. The function of miR-214–3p in OA, as well as the interaction between miR-214–3p and its downstream mRNA target (IKBKB), was evaluated by western blotting, immunofluorescence, qRT-PCR and luciferase assay. Mice models were introduced to examine the function and mechanism of miR-214–3p in OA in vivo.Findings:In our study, we found that miR-214–3p, while being down-regulated in inflamed chondrocytes and OA cartilage, regulated ECM metabolism and cell apoptosis in the cartilage. Mechanically, the protective effect of miR-214–3p downregulated the IKK-β expression and led to the dysfunction of NF-κB signaling pathway. Furthermore, intra-articular injection of miR-214–3p antagomir in mice joints triggered spontaneous cartilage loss while miRNA-214–3p agomir alleviated OA in the experimental mouse models.Interpretation:Decreased miR-214–3p activates the NF-κB signaling pathway and aggravates OA development through targeting IKKβ, suggesting miR-214–3p may be a novel therapeutic target for OA.

Item Type: Article
Authors/Creators:Cao, Y and Tang, S and Nie, X and Zhou, Z and Ruan, G and Han, W and Zhu, Z and Ding, C
Keywords: osteoarthritis, miR-214-3p, NF-kB, IKKb
Journal or Publication Title: EBioMedicine
Publisher: Elsevier BV
ISSN: 2352-3964
DOI / ID Number: 10.1016/j.ebiom.2021.103283
Copyright Information:

Copyright 2021 The Authors. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/

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