Redox and NF-κB signaling in osteoarthritis

Abstract

Abstract Human cells have to deal with the constant production of reactive oxygen species (ROS). Although ROS overproduction might be harmful to cell biology, there are plenty of data showing that moderate levels of ROS control gene expression by maintaining redox signaling. Osteoarthritis (OA) is the most common joint disorder with a multi‐factorial etiology including overproduction of ROS. ROS overproduction in OA modifies intracellular signaling, chondrocyte life cycle, metabolism of cartilage matrix and contributes to synovial inflammation and dysfunction of the subchondral bone. In arthritic tissues, the NF‐&kgr;B signaling pathway can be activated by pro‐inflammatory cytokines, mechanical stress, and extracellular matrix degradation products. This activation results in regulation of expression of many cytokines, inflammatory mediators, transcription factors, and several matrix‐degrading enzymes. Overall, NF‐&kgr;B signaling affects cartilage matrix remodeling, chondrocyte apoptosis, synovial inflammation, and has indirect stimulatory effects on downstream regulators of terminal chondrocyte differentiation. Interaction between redox signaling and NF‐&kgr;B transcription factors seems to play a distinctive role in OA pathogenesis. Graphical abstract Figure. No caption available. HighlightsOA is characterized by elevated levels of ROS.ROS regulate cartilage metabolism, synovial inflammation and subchondral bone function.NF‐&kgr;B target gene expression leads to articular destruction.Interaction between ROS and NF‐&kgr;B plays a distinctive role in OA pathogenesis.