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The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast
Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilag...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131469/ https://www.ncbi.nlm.nih.gov/pubmed/25147440 http://dx.doi.org/10.1155/2014/759028 |
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author | Chen, Yi-Te Hou, Chun-Han Hou, Sheng-Mou Liu, Ju-Fang |
author_facet | Chen, Yi-Te Hou, Chun-Han Hou, Sheng-Mou Liu, Ju-Fang |
author_sort | Chen, Yi-Te |
collection | PubMed |
description | Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG) binds to the EGF receptor (EGFR) and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs) remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis. |
format | Online Article Text |
id | pubmed-4131469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-41314692014-08-21 The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast Chen, Yi-Te Hou, Chun-Han Hou, Sheng-Mou Liu, Ju-Fang Mediators Inflamm Research Article Osteoarthritis (OA) belongs to a group of degenerative diseases. Synovial inflammation, cartilage abrasion, and subchondral sclerosis are characteristics of OA. Researchers do not fully understand the exact etiology of OA. However, matrix metalloproteinases (MMPs), which are responsible for cartilage matrix degradation, play a pivotal role in the progression of OA. Amphiregulin (AREG) binds to the EGF receptor (EGFR) and activates downstream proteins. AREG is involved in a variety of pathological processes, such as the development of tumors, inflammatory diseases, and rheumatoid arthritis. However, the relationship between AREG and MMP-13 in OA synovial fibroblasts (SFs) remains unclear. We investigated the signaling pathway involved in AREG-induced MMP-13 production in SFs. AREG caused MMP-13 production in a concentration- and time-dependent manner. The results of using pharmacological inhibitors and EGFR siRNA to block EGFR revealed that the EGFR receptor was involved in the AREG-mediated upregulation of MMP-13. AREG-mediated MMP-13 production was attenuated by PI3K and Akt inhibitors. The stimulation of cells by using AREG activated p65 phosphorylation and p65 translocation from the cytosol to the nucleus. Our results provide evidence that AREG acts through the EGFR and activates PI3K, Akt, and finally NF-kappaB on the MMP-13 promoter, thus contributing to cartilage destruction during osteoarthritis. Hindawi Publishing Corporation 2014 2014-07-24 /pmc/articles/PMC4131469/ /pubmed/25147440 http://dx.doi.org/10.1155/2014/759028 Text en Copyright © 2014 Yi-Te Chen et al. https://creativecommons.org/licenses/by/3.0/ 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 Chen, Yi-Te Hou, Chun-Han Hou, Sheng-Mou Liu, Ju-Fang The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title | The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title_full | The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title_fullStr | The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title_full_unstemmed | The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title_short | The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast |
title_sort | effects of amphiregulin induced mmp-13 production in human osteoarthritis synovial fibroblast |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4131469/ https://www.ncbi.nlm.nih.gov/pubmed/25147440 http://dx.doi.org/10.1155/2014/759028 |
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