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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...

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Autores principales: Chen, Yi-Te, Hou, Chun-Han, Hou, Sheng-Mou, Liu, Ju-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
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.
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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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