The effects of Amphiregulin induced mmp-13 production in human osteoarthritis synovial fibroblast
Journal
Mediators of Inflammation
Journal Volume
2014
Date Issued
2014
Author(s)
Abstract
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. ? 2014 Yi-Te Chen et al.
SDGs
Other Subjects
amphiregulin; collagenase 3; epidermal growth factor receptor; immunoglobulin enhancer binding protein; phosphatidylinositol 3 kinase inhibitor; protein kinase B inhibitor; small interfering RNA; synaptotagmin I; amphiregulin; collagenase 3; Article; controlled study; cytosol; enzyme induction; enzyme synthesis; fibroblast; gene expression; human; human cell; human tissue; molecular pathology; osteoarthritis; priority journal; promoter region; protein expression; protein function; protein localization; protein phosphorylation; RNA extraction; signal transduction; synovium; cell culture; cytology; drug effect; fibroblast; metabolism; osteoarthritis; synovium; Amphiregulin; Cells, Cultured; Fibroblasts; Humans; Matrix Metalloproteinase 13; Osteoarthritis; Synovial Membrane
Publisher
Hindawi Publishing Corporation
Type
journal article