8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL
2018
Abstract
Osteoclastsare
multinucleated giant cells
differentiatedfrom monocyte-macrophage-lineage cells under stimulation of receptor activator of nuclear factor κ-B (
RANK)
ligand(
RANKL) produced by osteoblasts and
osteocytes. Although it has been reported that nitric oxide (NO) and reactive oxygen species (ROS) are involved in this process, the mechanism by which these labile molecules promote
osteoclast
differentiationare not fully understood. In this study, we investigated the formation and function of 8-
nitro-cGMP, a downstream molecule of NO and ROS, in the process of
osteoclast
differentiationin vitro . 8-
Nitro-cGMP was detected in mouse bone marrow macrophages and
osteoclasts
differentiatedfrom macrophages in the presence of
RANKL. Inhibition of NO synthase suppressed the formation of 8-
nitro-cGMP as well as
RANKL-induced
osteoclast
differentiationfrom macrophages. On the other hand,
RANKL-induced
osteoclast
differentiationwas promoted by addition of 8-
nitro-cGMP to the cultures. In addition, 8-
nitro-cGMP enhanced the mRNA expression of RANK, the receptor for
RANKL. However,
8-bromo-cGMP, a membrane-permeable derivative of cGMP, did not have an effect on either
RANKL-induced
osteoclast
differentiationor expression of the RANK gene. These results suggest that 8-
nitro-cGMP is a novel positive regulator of
osteoclast
differentiation, which might help to explain the roles of NO and ROS in
osteoclast
differentiation.
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