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Resistin enhances IL‐1β and TNF‐α expression in human osteoarthritis synovial fibroblasts by inhibiting miR‐149 expression via the MEK and ERK pathways
Author(s) -
Chen WeiCheng,
Lu YungChang,
Kuo ShuJui,
Lin ChihYang,
Tsai ChunHao,
Liu ShanChi,
Chen YenLing,
Wang ShihWei,
Tang ChihHsin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202001071r
Subject(s) - mapk/erk pathway , tumor necrosis factor alpha , cancer research , resistin , expression (computer science) , microrna , osteoarthritis , microbiology and biotechnology , medicine , chemistry , signal transduction , biology , pathology , gene , leptin , adipokine , computer science , biochemistry , alternative medicine , programming language , obesity
Resistin is a cysteine‐rich adipokine that promotes the release of inflammatory cytokines, particularly interleukin 1 beta (IL‐1β) and tumor necrosis factor alpha (TNF‐α), which are critical pro‐inflammatory mediators in osteoarthritis (OA) pathogenesis. We describe evidence of significantly higher levels of resistin, IL‐1β, and TNF‐α expression in OA knee synovial tissue compared with that from non‐OA knees. Resistin‐induced enhancement of IL‐1β and TNF‐α expression in human OA synovial fibroblasts (OASFs) were attenuated by MEK and ERK inhibitors, as well as their respective siRNAs. Our data reveal that resistin enhances the expression of TNF‐α and IL‐1β in OASFs by inhibiting miR‐149 expression via MEK and ERK signaling. Our findings elucidate the inter‐relationships between resistin and pro‐inflammatory mediators during OA pathogenesis and could help to facilitate the development of synovium‐targeted therapy in OA.