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Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140
Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matr...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935446/ https://www.ncbi.nlm.nih.gov/pubmed/31915516 http://dx.doi.org/10.1155/2019/9705929 |
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author | Zhang, Yijian Lin, Jun Zhou, Xinfeng Chen, Xi Chen, Angela Carley Pi, Bin Pan, Guoqing Pei, Ming Yang, Huilin Liu, Tao He, Fan |
author_facet | Zhang, Yijian Lin, Jun Zhou, Xinfeng Chen, Xi Chen, Angela Carley Pi, Bin Pan, Guoqing Pei, Ming Yang, Huilin Liu, Tao He, Fan |
author_sort | Zhang, Yijian |
collection | PubMed |
description | Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1β-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1β stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA. |
format | Online Article Text |
id | pubmed-6935446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-69354462020-01-08 Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 Zhang, Yijian Lin, Jun Zhou, Xinfeng Chen, Xi Chen, Angela Carley Pi, Bin Pan, Guoqing Pei, Ming Yang, Huilin Liu, Tao He, Fan Oxid Med Cell Longev Research Article Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage, which is involved in the imbalance between extracellular matrix (ECM) synthesis and degradation. MicroRNA-140-5p (miR-140) is specifically expressed in cartilage and plays an important role in OA-induced matrix degradation. The aim of this study was to investigate (1) whether intra-articular injection of melatonin could ameliorate surgically induced OA in mice and (2) whether melatonin could regulate matrix-degrading enzymes at the posttranscriptional level by targeting miR-140. In an in vitro OA environment induced by interleukin-1 beta (IL-1β), melatonin treatment improved cell proliferation of human chondrocytes, promoted the expression of cartilage ECM proteins (e.g., type II collagen and aggrecan), and inhibited the levels of IL-1β-induced proteinases, such as matrix metalloproteinase 9 (MMP9), MMP13, ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), and ADAMTS5. Both the microarray and polymerase chain reaction (PCR) experiments revealed that miR-140 was a melatonin-responsive microRNA and melatonin upregulated miR-140 expression, which was suppressed by IL-1β stimulation. In vivo experiments demonstrated that intra-articular injection of melatonin prevented disruptions of cartilage matrix homeostasis and successfully alleviated the progression of surgery-induced OA in mice. Transfection of miR-140 antagomir completely counteracted the antiarthritic effects of melatonin by promoting matrix destruction. Our findings demonstrate that melatonin protects the articular cartilage from OA-induced degradation by targeting miR-140, and intra-articular administration of melatonin may benefit patients suffering from OA. Hindawi 2019-12-14 /pmc/articles/PMC6935446/ /pubmed/31915516 http://dx.doi.org/10.1155/2019/9705929 Text en Copyright © 2019 Yijian Zhang et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Zhang, Yijian Lin, Jun Zhou, Xinfeng Chen, Xi Chen, Angela Carley Pi, Bin Pan, Guoqing Pei, Ming Yang, Huilin Liu, Tao He, Fan Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title | Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title_full | Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title_fullStr | Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title_full_unstemmed | Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title_short | Melatonin Prevents Osteoarthritis-Induced Cartilage Degradation via Targeting MicroRNA-140 |
title_sort | melatonin prevents osteoarthritis-induced cartilage degradation via targeting microrna-140 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935446/ https://www.ncbi.nlm.nih.gov/pubmed/31915516 http://dx.doi.org/10.1155/2019/9705929 |
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