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Mediators of Inflammation
Volume 2014 (2014), Article ID 759028, 12 pages
Research Article

The Effects of Amphiregulin Induced MMP-13 Production in Human Osteoarthritis Synovial Fibroblast

1Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-chang Road, Shi-lin District, Taipei 11101, Taiwan
2Department of Orthopedic Surgery, National Taiwan University Hospital, No.1, Section 1, Ren-ai Road, Zhong-zheng District, Taipei 10051, Taiwan
3Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Road, Shi-lin District, Taipei 11101, Taiwan

Received 30 April 2014; Revised 27 June 2014; Accepted 7 July 2014; Published 24 July 2014

Academic Editor: Luca Cantarini

Copyright © 2014 Yi-Te Chen et al. 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.


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.