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

Citation

Cao, Y and Tang, S and Nie, X and Zhou, Z and Ruan, G and Han, W and Zhu, Z and Ding, C, Decreased miR-214-3p activates NF-κB pathway and aggravates osteoarthritis progression, EBioMedicine, 65 pp. 1-11. ISSN 2352-3964 (2021) [Refereed Article]


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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/

DOI: doi:10.1016/j.ebiom.2021.103283

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-2143p as an important regulator of OA.

Methods: qRT-PCR and in situ hybridization were used to detect the expression level of miR-2143p. The function of miR-2143p in OA, as well as the interaction between miR-2143p 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-2143p in OA in vivo.

Findings: In our study, we found that miR-2143p, 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-2143p downregulated the IKK-β expression and led to the dysfunction of NF-κB signaling pathway. Furthermore, intra-articular injection of miR-2143p antagomir in mice joints triggered spontaneous cartilage loss while miRNA-2143p agomir alleviated OA in the experimental mouse models.

Interpretation: Decreased miR-2143p activates the NF-κB signaling pathway and aggravates OA development through targeting IKKβ, suggesting miR-2143p may be a novel therapeutic target for OA.

Item Details

Item Type:Refereed Article
Keywords:osteoarthritis, miR-214-3p, NF-kB, IKKb
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Orthopaedics
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Ding, C (Professor Chang-Hai Ding)
ID Code:146219
Year Published:2021
Web of Science® Times Cited:7
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-08-25
Last Modified:2021-09-29
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