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]
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/
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:||Refereed Article|
|Keywords:||osteoarthritis, miR-214-3p, NF-kB, IKKb|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Clinical sciences|
|Objective Group:||Clinical health|
|Objective Field:||Diagnosis of human diseases and conditions|
|UTAS Author:||Ding, C (Professor Chang-Hai Ding)|
|Web of Science® Times Cited:||21|
|Deposited By:||Menzies Institute for Medical Research|
|Downloads:||30 View Download Statistics|
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