Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression
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(miR...
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doaj-a585cddb66fd4d29a547eca4b6a5d91b2021-03-13T04:24:29ZengElsevierEBioMedicine2352-39642021-03-0165103283Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progressionYumei Cao0Su'an Tang1Xiaoyu Nie2Zuoqing Zhou3Guangfeng Ruan4Weiyu Han5Zhaohua Zhu6Changhai Ding7Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Rheumatology and Immunology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Centre of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Corresponding authors.Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Centre of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Department of Orthopedics, The First Affiliated Hospital, Shaoyang University, Shaoyang, Hunan, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Centre of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaClinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Corresponding authors.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. Funding: This study was financially supported by grants from the National Natural Science Foundation of China (81,773,532, 81,974,342).http://www.sciencedirect.com/science/article/pii/S2352396421000761OsteoarthritismiR-214–3pNF-κBIKKβ |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yumei Cao Su'an Tang Xiaoyu Nie Zuoqing Zhou Guangfeng Ruan Weiyu Han Zhaohua Zhu Changhai Ding |
spellingShingle |
Yumei Cao Su'an Tang Xiaoyu Nie Zuoqing Zhou Guangfeng Ruan Weiyu Han Zhaohua Zhu Changhai Ding Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression EBioMedicine Osteoarthritis miR-214–3p NF-κB IKKβ |
author_facet |
Yumei Cao Su'an Tang Xiaoyu Nie Zuoqing Zhou Guangfeng Ruan Weiyu Han Zhaohua Zhu Changhai Ding |
author_sort |
Yumei Cao |
title |
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression |
title_short |
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression |
title_full |
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression |
title_fullStr |
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression |
title_full_unstemmed |
Decreased miR-214–3p activates NF-κB pathway and aggravates osteoarthritis progression |
title_sort |
decreased mir-214–3p activates nf-κb pathway and aggravates osteoarthritis progression |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-03-01 |
description |
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. Funding: This study was financially supported by grants from the National Natural Science Foundation of China (81,773,532, 81,974,342). |
topic |
Osteoarthritis miR-214–3p NF-κB IKKβ |
url |
http://www.sciencedirect.com/science/article/pii/S2352396421000761 |
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