Resistin enhances IL‐1β and TNF‐α expression in human osteoarthritis synovial fibroblasts by inhibiting miR‐149 expression via the MEK and ERK pathways
Wei‐Cheng Chen, Yung‐Chang Lu, Shu‐Jui Kuo, Chih‐Yang Lin, Chun‐Hao Tsai, Shan‐Chi Liu, Yen‐Ling Chen, Shih‐Wei Wang, Chih‐Hsin Tang
Abstract
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.