PMID- 25147440 OWN - NLM STAT- MEDLINE DCOM- 20150515 LR - 20211025 IS - 1466-1861 (Electronic) IS - 0962-9351 (Print) IS - 0962-9351 (Linking) VI - 2014 DP - 2014 TI - The effects of amphiregulin induced MMP-13 production in human osteoarthritis synovial fibroblast. PG - 759028 LID - 10.1155/2014/759028 [doi] LID - 759028 AB - 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. FAU - Chen, Yi-Te AU - Chen YT AD - Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-chang Road, Shi-lin District, Taipei 11101, Taiwan. FAU - Hou, Chun-Han AU - Hou CH AD - Department of Orthopedic Surgery, National Taiwan University Hospital, No.1, Section 1, Ren-ai Road, Zhong-zheng District, Taipei 10051, Taiwan. FAU - Hou, Sheng-Mou AU - Hou SM AD - Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wen-chang Road, Shi-lin District, Taipei 11101, Taiwan. FAU - Liu, Ju-Fang AU - Liu JF AD - Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Road, Shi-lin District, Taipei 11101, Taiwan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140724 PL - United States TA - Mediators Inflamm JT - Mediators of inflammation JID - 9209001 RN - 0 (Amphiregulin) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) SB - IM MH - Amphiregulin/*pharmacology MH - Cells, Cultured MH - Fibroblasts/drug effects/*metabolism MH - Humans MH - Matrix Metalloproteinase 13/*metabolism MH - Osteoarthritis/*metabolism MH - Synovial Membrane/*cytology PMC - PMC4131469 EDAT- 2014/08/26 06:00 MHDA- 2015/05/16 06:00 PMCR- 2014/07/24 CRDT- 2014/08/23 06:00 PHST- 2014/04/30 00:00 [received] PHST- 2014/06/27 00:00 [revised] PHST- 2014/07/07 00:00 [accepted] PHST- 2014/08/23 06:00 [entrez] PHST- 2014/08/26 06:00 [pubmed] PHST- 2015/05/16 06:00 [medline] PHST- 2014/07/24 00:00 [pmc-release] AID - 10.1155/2014/759028 [doi] PST - ppublish SO - Mediators Inflamm. 2014;2014:759028. doi: 10.1155/2014/759028. Epub 2014 Jul 24.