the synovial level, we also studied potential effects
directly at the bone level by employing an in vitro
approach. In these studies, corticosteroids (DEX)
changed the phenotype of TNF-primed osteoblasts
through down-regulation of RANKL expression without
influencing OPG expression. This is an interesting find-
ing in light of the fact that TNF is considered a central
mediator for bone destruction in RA (33). We also
confirm previous data showing an increase of the
RANKL:OPG ratio in the absence of the inflammatory
stimulus. It might be that local delivery of cortico-
steroids at the site of inflammation in acute, severe
flares of disease is a valuable therapeutic choice to
combat inflammation and bone destruction without the
increased risk of osteoporosis seen with long-term sys-
temic administration of high doses. Further studies are
needed to identify the exact molecular mechanism un-
derlying the bone-protective effect of corticosteroids in
the presence of an inflammatory stimulus, but recent
findings regarding the relevance of the cyclooxygenase 2
(COX-2) pathway both in bone biology (34,35) and in
RA pathogenesis (36) might offer a clue. Corticosteroids
are able to decrease COX-2 expression in osteoblast
cultures (37) as well as in the rheumatoid synovium (38),
thus potentially modulating COX-2–dependent RANKL
The present study demonstrates that in inflam-
matory arthritis, therapy with intraarticular cortico-
steroids modulates the RANKL/OPG system toward a
bone-protective effect. We propose this mechanism as
an interesting potential molecular explanation for the
mode of action of intraarticular corticosteroids.
We thank Associate Professor Robert Harris for lin-
guistic advice and Marianne Engstrom for excellent technical
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