Background/Aims@#The present study aimed to investigate whether
tocotrienol regulates
interleukin 17 (
IL-17)-induced
osteoclastogenesis in
rheumatoid arthritis (RA). @*
Methods@#We evaluated the effect of
tocotrienol on
IL-17-induced
receptor activator of nuclear factor kappa B ligand (RANKL)
production using RA
fibroblast-like
synoviocyte (FLS), together with
real-time polymerase chain reaction and
enzyme-linked immunosorbent assay.
Osteoclast differentiation was confirmed after culturing
IL-17-treated RA FLS and
Th17 cells with
tocotrienol and
monocytes. We analyzed the suppressive effect of
tocotrienol on
Th17 cells percentage or Th17-
cytokine levels among
peripheral blood mononuclear cells using
flow cytometry. @*Results@#We found that
IL-17 stimulated FLS to produce RANKL and
tocotrienol decreased this
IL-17-induced RANKL
production.
Tocotrienol decreased the
IL-17-induced activation of
mammalian target of rapamycin,
extracellular signal-regulated kinase, and inhibitor of kappa B-alpha. When
monocytes were incubated with
IL-17, RANKL,
IL-17-treated FLS or
Th17 cells,
osteoclasts were differentiated and
tocotrienol decreased this
osteoclast differentiation.
Tocotrienol reduced
Th17 cell differentiation and the
production of
IL-17 and sRANKL; however,
tocotrienol did not
affect Treg cell differentiation. @*Conclusions@#
Tocotrienol inhibited
IL-17- activated RANKL
production in RA FLS and
IL-17-activated
osteoclast formation. In addition,
tocotrienol reduced Th17 differentiation. Therefore,
tocotrienol could be a new
therapeutic choice to treat
bone destructive processes in RA.