Inhibition of NF‐[kappa]B activation in osteoclasts by eicosapentaenoic acid

Abstract

NF-κB is a transcriptional activator of many genes. It is activated after receptor binding of a mediator such as the receptor activator of NF-κB ligand (RANKL) or TNF-α. RANKL activates distinct signaling pathways (such as NF-κB) during osteoclastogenesis and bone resorption. Eicosapentaenoic acid (EPA) is a fatty acid known to inhibit NF-κB activation in certain cells types, but the effects have not been investigated in osteoclasts. We investigated the effects of EPA on RANKL-induced differentiation of RAW264.7 monocyte/macrophage cells, and on NF-κB activation in differentiated RAW264.7 cells exposed to TNF-α or modeled microgravity using a High-Aspect Ratio Vessel (HARV). RAW264.7 cells were incubated with or without 50 μM EPA for 24 h and then differentiated into osteoclast-like cells in the presence of 50 ng/mL RANKL. In a separate experiment, differentiated RAW264.7 cells were treated with 50 μM EPA for 24 h before they were exposed to 0.2 μg/mL TNF-α or modeled microgravity in a HARV. EPA dose-dependently inhibited the RANKL-induced differentiation of RAW264.7 cells. A 24-h incubation with EPA also decreased activation of NF-κB induced by TNF-α or modeled microgravity. These data provide in vitro evidence for the potential of EPA to provide a countermeasure to mitigate bone loss associated with space flight. This study was supported by NASA.