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Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis
AIMS: The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). METHODS: TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (U...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The British Editorial Society of Bone & Joint Surgery
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572806/ https://www.ncbi.nlm.nih.gov/pubmed/33231490 http://dx.doi.org/10.1302/2046-3758.910.BJR-2020-0140.R1 |
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author | Zhang, Aobo Ma, Shixing Yuan, Lingyu Wu, Shichao Liu, Shaopeng Wei, Xiang Chen, Lei Ma, Chuan Zhao, Huaqiang |
author_facet | Zhang, Aobo Ma, Shixing Yuan, Lingyu Wu, Shichao Liu, Shaopeng Wei, Xiang Chen, Lei Ma, Chuan Zhao, Huaqiang |
author_sort | Zhang, Aobo |
collection | PubMed |
description | AIMS: The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). METHODS: TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR. RESULTS: UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05). CONCLUSION: MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: Bone Joint Res 2020;9(10):689–700. |
format | Online Article Text |
id | pubmed-7572806 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The British Editorial Society of Bone & Joint Surgery |
record_format | MEDLINE/PubMed |
spelling | pubmed-75728062020-10-30 Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis Zhang, Aobo Ma, Shixing Yuan, Lingyu Wu, Shichao Liu, Shaopeng Wei, Xiang Chen, Lei Ma, Chuan Zhao, Huaqiang Bone Joint Res Arthritis AIMS: The study aimed to determine whether the microRNA miR21-5p (MiR21) mediates temporomandibular joint osteoarthritis (TMJ-OA) by targeting growth differentiation factor 5 (Gdf5). METHODS: TMJ-OA was induced in MiR21 knockout (KO) mice and wild-type (WT) mice by a unilateral anterior crossbite (UAC) procedure. Mouse tissues exhibited histopathological changes, as assessed by: Safranin O, toluidine blue, and immunohistochemistry staining; western blotting (WB); and quantitative real-time polymerase chain reaction (RT-qPCR). Mouse condylar chondrocytes were transfected with a series of MiR21 mimic, MiR21 inhibitor, Gdf5 siRNA (si-GDF5), and flag-GDF5 constructs. The effects of MiR-21 and Gdf5 on the expression of OA related molecules were evaluated by immunofluorescence, alcian blue staining, WB, and RT-qPCR. RESULTS: UAC altered the histological structure and extracellular matrix content of cartilage in the temporomandibular joint (TMJ), and KO of MiR21 alleviated this effect (p < 0.05). Upregulation of MiR21 influenced the expression of TMJ-OA related molecules in mandibular condylar chondrocytes via targeting Gdf5 (p < 0.05). Gdf5 overexpression significantly decreased matrix metalloproteinase 13 (MMP13) expression (p < 0.05) and reversed the effects of MiR21 (p < 0.05). CONCLUSION: MiR21, which acts as a critical regulator of Gdf5 in chondrocytes, regulates TMJ-OA related molecules and is involved in cartilage matrix degradation, contributing to the progression of TMJ-OA. Cite this article: Bone Joint Res 2020;9(10):689–700. The British Editorial Society of Bone & Joint Surgery 2020-10-16 /pmc/articles/PMC7572806/ /pubmed/33231490 http://dx.doi.org/10.1302/2046-3758.910.BJR-2020-0140.R1 Text en © 2020 Author(s) et al. https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (CC BY-NC-ND 4.0) licence, which permits the copying and redistribution of the work only, and provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc-nd/4.0/ See https://creativecommons.org/licenses/by-nc-nd/4.0/. |
spellingShingle | Arthritis Zhang, Aobo Ma, Shixing Yuan, Lingyu Wu, Shichao Liu, Shaopeng Wei, Xiang Chen, Lei Ma, Chuan Zhao, Huaqiang Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title | Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title_full | Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title_fullStr | Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title_full_unstemmed | Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title_short | Knockout of miR-21-5p alleviates cartilage matrix degradation by targeting Gdf5 in temporomandibular joint osteoarthritis |
title_sort | knockout of mir-21-5p alleviates cartilage matrix degradation by targeting gdf5 in temporomandibular joint osteoarthritis |
topic | Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572806/ https://www.ncbi.nlm.nih.gov/pubmed/33231490 http://dx.doi.org/10.1302/2046-3758.910.BJR-2020-0140.R1 |
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