Premium
Inhibition of NF‐[kappa]B activation in osteoclasts by eicosapentaenoic acid
Author(s) -
Zwart Sara R.,
Gonda Steve R.,
Bolster Douglas R.,
Smith Scott M.
Publication year - 2006
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/fasebj.20.4.a561-b
Subject(s) - rankl , osteoclast , chemistry , activator (genetics) , bone resorption , eicosapentaenoic acid , receptor , microbiology and biotechnology , nf κb , monocyte , medicine , biochemistry , endocrinology , signal transduction , biology , fatty acid , polyunsaturated fatty acid
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.